Reactive oxygen species are closely related to tumor development.In recent years,reactive oxygen species has become a hot spot in tumor therapy,and many natural substances in nature contain compound components with an...Reactive oxygen species are closely related to tumor development.In recent years,reactive oxygen species has become a hot spot in tumor therapy,and many natural substances in nature contain compound components with anti-tumor effects.However,there is a lack of discussion on the synergistic anti-tumor effects of natural products in combination with chemotherapeutic drugs through reactive oxygen species.The terms“natural products”,“reactive oxygen species”,“anti-tumor”,and“chemotherapy”were used to identify the synergistic effects of natural products.We conducted a systematic literature search in PubMed and Web of Science databases for relevant research articles and reviews published in recent years.We systematically summarized the studies related to anti-tumor active ingredients in natural compounds in the field of reactive oxygen species in recent years.A total of 77 relevant literatures were included.Among them,45 literatures containing various natural products such as terpenoids,flavonoids,alkaloids,etc.exert anti-tumor effects by regulating reactive oxygen species levels,and 32 literatures regarding adjunctive role of natural products in anti-tumor therapy.In this study,we found that natural products exert anti-tumor effects by elevating reactive oxygen species levels.It provides strong theoretical support for future clinical studies.展开更多
DNA guanine(G)-quadruplexes(G4s)are unique secondary structures formed by two or more stacked Gtetrads in G-rich DNA sequences.These structures have been found to play a crucial role in highly transcribed genes,especi...DNA guanine(G)-quadruplexes(G4s)are unique secondary structures formed by two or more stacked Gtetrads in G-rich DNA sequences.These structures have been found to play a crucial role in highly transcribed genes,especially in cancer-related oncogenes,making them attractive targets for cancer therapeutics.Significantly,targeting oncogene promoter G4 structures has emerged as a promising strategy to address the challenge of undruggable and drug-resistant proteins,such as MYC,BCL2,KRAS,and EGFR.Natural products have long been an important source of drug discovery,particularly in the fields of cancer and infectious diseases.Noteworthy progress has recently been made in the discovery of naturally occurring DNA G4-targeting drugs.Numerous DNA G4s,such as MYC-G4,BCL2-G4,KRAS-G4,PDGFR-b-G4,VEGF-G4,and telomeric-G4,have been identified as potential targets of natural products,including berberine,telomestatin,quindoline,sanguinarine,isaindigotone,and many others.Herein,we summarize and evaluate recent advancements in natural and nature-derived DNA G4 binders,focusing on understanding the structural recognition of DNA G4s by small molecules derived from nature.We also discuss the challenges and opportunities associated with developing drugs that target DNA G4s.展开更多
The isolation of minor components from complex natural product matrices presents a significant challenge in the field of purification science due to their low concentrations and the presence of structurally similar co...The isolation of minor components from complex natural product matrices presents a significant challenge in the field of purification science due to their low concentrations and the presence of structurally similar compounds.This study introduces an optimized twin-column recycling chromatography method for the efficient and simultaneous purification of these elusive constituents.By introducing water at a small flowing rate between the twin columns,a step solvent gradient is created,by which the leading edge of concentration band would migrate at a slower rate than the trailing edge as it flowing from the upstream to downstream column.Hence,the band broadening is counterbalanced,resulting in an enrichment effect for those minor components in separation process.Herein,two target substances,which showed similar peak position in high performance liquid chromatography(HPLC)and did not exceed 1.8%in crude paclitaxel were selected as target compounds for separation.By using the twin-column recycling chromatography with a step solvent gradient,a successful purification was achieved in getting the two with the purity almost 100%.We suggest this method is suitable for the separation of most components in natural produces,which shows higher precision and recovery rate compared with the common lab-operated separation ways for natural products(thin-layer chromatography and prep-HPLC).展开更多
Microcirculatory disturbances are complex processes caused by many factors,including abnormal vasomotor responses,decreased blood flow velocity,vascular endothelial cell injury,altered leukocyte and endothelial cell i...Microcirculatory disturbances are complex processes caused by many factors,including abnormal vasomotor responses,decreased blood flow velocity,vascular endothelial cell injury,altered leukocyte and endothelial cell interactions,plasma albumin leakage,microvascular hemorrhage,and thrombosis.These disturbances involve multiple mechanisms and interactions among mechanisms that can include energy metabolism,the mitochondrial respiratory chain,oxidative stress,inflammatory factors,adhesion molecules,the cytoskeleton,vascular endothelial cells,caveolae,cell junctions,the vascular basement membrane,neutrophils,monocytes,and platelets.In clinical practice,aside from drugs that target abnormal vasomotor responses and platelet adhesion,there continues to be a lack of multi-target drugs that can regulate the complex mechanistic links and interactions underlying microcirculatory disturbances.Natural products have demonstrated obvious positive therapeutic effects in treating ischemia/reperfusion(I/R)-and lipopolysaccharide(LPS)-induced microcirculatory disturbances.In recent years,numerous research papers on the improvement of microcirculatory function by natural products have been published in international journals.In 2008 and 2017,the first listed author of this review was invited to publish reviews in the journal of Pharmacology&Therapeutics on the improvement of microcirculatory disturbances and organ injury induced by I/R using Salvia miltiorrhiza ingredients and other natural components of compounded Chinese medicine,respectively.This review systematically summarizes the effects,targets of action,and mechanisms of natural products regarding improving I/R-and LPSinduced microcirculatory disturbances and tissue injury.Based on this summary,scientific proposals are suggested for the discovery of new drugs to improve microcirculatory disturbances in disease.展开更多
Marine natural products(MNPs)are valuable resources for drug development.To date,17 drugs from marine sources are in clinical use,and 33 pharmaceutical compounds are in clinical trials.Presently the success of drug de...Marine natural products(MNPs)are valuable resources for drug development.To date,17 drugs from marine sources are in clinical use,and 33 pharmaceutical compounds are in clinical trials.Presently the success of drug development from the marine resources is higher than the industry average.It is a feasible strategy to conduct the discovery of druglead compounds based on marine chemical ecology by fully exploiting the pharmacological potential of marine chemical defense matters.In the search for bioactive MNPs,our group has constructed a biological resources library including more than 1500 strains of fungi.Focusing on the strategy of Blue Drug Library,we have discovered a series of novel MNPs with abundant biological functions.Highly efficient and scalable total synthesis of(+)-aniduquinolone A(44)and pesimquinolone I(48)have been completed,which will facilitate access to sufficient quantities of candidates for in vivo pharmacological and toxicological studies.As a nucleoprotein(NP)inhibitor,QLA(75)possesses significant anti-influenza A virus(IAV)activities both in vitro and in vivo.CHNQD-00803(76)is a potent and selective AMP-activated kinase(AMPK)activator that can effectively inhibit metabolic disorders and metabolic dysfunction-associated steatohepatitis(MASH)progression.Moreover,we identified two new candidate molecules with potent anti-hepatocellular carcinoma effects.Particularly,as a natural guanine-nucleotide exchange factors for ADP-ribosylation factor GTPases(Arf-GEFs)inhibitor prodrug,CHNQD-01255(78)is qualified to be developed as a targeted candidate anticancer drug,which may be promising to apply for cancer immunotherapy.Hence,it is evident that MNPs play an important role in drug development.展开更多
Hepatocellular carcinoma(HCC)remains a prevalent and challenging malignancy globally,characterized by its numerous causal factors and generally unfavorable prognosis.In the relentless pursuit of effective treatment mo...Hepatocellular carcinoma(HCC)remains a prevalent and challenging malignancy globally,characterized by its numerous causal factors and generally unfavorable prognosis.In the relentless pursuit of effective treatment modalities,natural products have emerged as a promising and relatively non-toxic alternative,garnering significant interest.The integration of natural products with contemporary medical research has yielded encouraging therapeutic outcomes in the management of HCC.This review offers a comprehensive overview of the causal factors underlying HCC,and the diverse treatment options available,and highlights the advancements made by natural products in anti-HCC research.Particularly,we provide an outline of the various types of natural products,their corresponding nomenclature,target molecules,and mechanisms of action that exhibit anti-HCC activities.Natural products are anticipated to play a pivotal role in future comprehensive treatment plans for liver cancer,potentially offering patients improved survival rates and an enhanced quality of life.展开更多
BACKGROUND Type 2 diabetes(T2D)is a metabolic disease of impaired glucose utilization and a major cause of cardiovascular disease(CVD).The pathogenesis of both diseases shares common risk factors and mechanisms,and bo...BACKGROUND Type 2 diabetes(T2D)is a metabolic disease of impaired glucose utilization and a major cause of cardiovascular disease(CVD).The pathogenesis of both diseases shares common risk factors and mechanisms,and both are significant contributors to global morbidity and mortality.Supplements of natural products for T2D mellitus(T2DM)and CVD can be seen as a potential preventive and effective therapeutic strategy.AIM To critically evaluate the therapeutic potential of natural products in T2D and coronary artery disease(CAD).METHODS By using specific keywords,we strategically searched the PubMed database.Randomized controlled trials(RCTs)were searched as the primary focus that examined the effect of natural products on glycemic control,oxidative stress,and antioxidant levels.We focused on outcomes such as low blood glucose levels,adjustment on markers of oxidative stress and antioxidants.After screening fulllength papers,we included 9 RCTs in our review that met our inclusion criteria.RESULTS In the literature search on the database,we found that various natural products like plant secondary metabolites play a diverse role in the management of CAD.American ginseng,sesame oil and cocoa flavanols proved effective in lowering blood glucose levels and controlling blood pressure,which are key factors in managing T2DM and CVD.In diabetic patients Melissa officinalis effectively reduce inflammation and shows diabetes prevention.Both fish oil and flaxseed oil reduced insulin levels and inflammatory markers,suggesting benefits for both conditions.The lipid profile and endothelial function were enhanced by Nigella sativa oil and Terminalia chebula,which is significant for the management of cardiovascular risk factors in T2DM.Additionally Bilberry extract also showed promise for improving glycemic control in patients with T2DM.CONCLUSION The high level of antioxidant,anti-inflammatory,and anti-angiogenic properties found in natural products makes them promising therapeutic options for the management of CAD,with the potential benefit of lowering the risk of CAD.展开更多
Esophageal cancer(ESC)is a malignant tumor that originates from the mucosal epithelium of the esophagus and is part of the digestive tract.Although the exact pathogenesis of ESC has not been fully elucidated,excessive...Esophageal cancer(ESC)is a malignant tumor that originates from the mucosal epithelium of the esophagus and is part of the digestive tract.Although the exact pathogenesis of ESC has not been fully elucidated,excessive oxidative stress is an important characteristic that leads to the development of many cancers.Abnormal expression of several proteins and transcription factors contributes to oxidative stress in ESCs,which alters the growth and proliferation of ESCs and promotes their metastasis.Natural compounds,including alkaloids,terpenes,polyphenols,and xanthine compounds,can inhibit reactive oxygen species production in ESCs.These compounds reduce oxidative stress levels and subsequently inhibit the oc-currence and progression of ESC through the regulation of targets and pathways such as the cytokine interleukins 6 and 10,superoxide dismutase,the NF-+ACY-kappa+ADs-B/MAPK pathway,and the mammalian Nrf2/ARE target pathway.Thus,targeting tumor oxidative stress has become a key focus in anti-ESC therapy.This review discusses the potential of Natural products(NPs)for treating ESCs and summarizes the application prospects of oxidative stress as a new target for ESC treatment.The findings of this review provide a reference for drug development targeting ESCs.Nonetheless,further high-quality studies will be necessary to determine the clinical efficacy of these various NPs.展开更多
It is important to study the effect of hydrate production on the physical and mechanical properties of low-permeability clayey–silty reservoirs for the largescale exploitation of hydrate reservoirs in the South China...It is important to study the effect of hydrate production on the physical and mechanical properties of low-permeability clayey–silty reservoirs for the largescale exploitation of hydrate reservoirs in the South China Sea.In this study,a multiphysical-field coupling model,combined with actual exploration drilling data and the mechanical experimental data of hydrate cores in the laboratory,was established to investigate the physical and mechanical properties of low-permeability reservoirs with different slope angles during 5-year hydrate production by the depressurization method via a horizontal well.The result shows that the permeability of reservoirs severely affects gas production rate,and the maximum gas production amount of a 20-m-long horizontal well can reach186.8 m3/day during the 5-year hydrate production.Reservoirs with smaller slope angles show higher gas production rates.The depressurization propagation and hydrate dissociation mainly develop along the direction parallel to the slope.Besides,the mean effective stress of reservoirs is concentrated in the near-wellbore area with the on-going hydrate production,and gradually decreases with the increase of the slope angle.Different from the effective stress distribution law,the total reservoir settlement amount first decreases and then increases with the increase of the slope angle.The maximum settlement of reservoirs with a 0°slope angle is up to 3.4 m,and the displacement in the near-wellbore area is as high as2.2 m after 5 years of hydrate production.It is concluded that the pore pressure drop region of low-permeability reservoirs in the South China Sea is limited,and various slope angles further lead to differences in effective stress and strain of reservoirs during hydrate production,resulting in severe uneven settlement of reservoirs.展开更多
Streptomyces is an important treasure trove for natural products discovery.In recent years,many scientists focused on the genetic modification and metabolic regulation of Streptomyces to obtain diverse bioactive compo...Streptomyces is an important treasure trove for natural products discovery.In recent years,many scientists focused on the genetic modification and metabolic regulation of Streptomyces to obtain diverse bioactive compounds with high yields.This review summarized the commonly used regulatory strategies for natural products discovery and overproduction in Streptomyces from three main aspects,including regulator-related strategies,promoter engineering,as well as other strategies employing transposons,signal factors,or feedback regulations.It is expected that the metabolic regulation network of Streptomyces will be elucidated more comprehensively to shed light on natural products research in the future.展开更多
Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year,with an estimated 5-year survival rate of 30%–35%after diagnosis.Hepatocellular carcinoma(HCC)constitutes...Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year,with an estimated 5-year survival rate of 30%–35%after diagnosis.Hepatocellular carcinoma(HCC)constitutes a significant subtype of liver cancer(approximate75%)and is considered primary liver cancer.Treatment for liver cancer mainly depends on the stage of its progression,where surgery including,hepatectomy and liver transplantation,and ablation and radiotherapy are the prime choice.For advanced liver cancer,various drugs and immunotherapy are used as first-line treatment,whereas second-line treatment includes chemotherapeutic drugs from natural and synthetic origins.Sorafenib and lenvatinib are first-line therapies,while regorafenib and ramucirumab are secondline therapy.Various metabolic and signaling pathways such as Notch,JAK/STAT,Hippo,TGF-β,and Wnt have played a critical role during HCC progression.Dysbiosis has also been implicated in liver cancer.Drug-induced toxicity is a key obstacle in the treatment of liver cancer,necessitating the development of effective and safe medications,with natural compounds such as resveratrol,curcumin,diallyl sulfide,and others emerging as promising anticancer agents.This review highlights the current status of liver cancer research,signaling pathways,therapeutic targets,current treatment strategies and the chemopreventive role of various natural products in managing liver cancer.展开更多
Diabetes mellitus(DM)is a complicated,globally expanding disease that is influenced by hereditary and environmental variables.Changes in modern society’s food choices,physical inactivity,and obesity are significant f...Diabetes mellitus(DM)is a complicated,globally expanding disease that is influenced by hereditary and environmental variables.Changes in modern society’s food choices,physical inactivity,and obesity are significant factors in the development of type 2 DM(T2DM).The association between changes in intestinal flora and numerous disorders,including obesity,diabetes,and cardiovascular diseases,has been studied in recent years.The purpose of this review is to analyze the mechanisms underlying the alteration of the diabetic patients’intestinal flora,as well as their therapeutic choices.Also included is a summary of the antidiabetic benefits of natural compounds demonstrated by studies.The short-chain fatty acids theory,the bile acid theory,and the endotoxin theory are all potential methods by which intestinal flora contributes to the establishment and progression of T2DM.Due to an intestinal flora imbalance,abnormalities in shortchain fatty acids and secondary bile acids have been found in diabetic patients.Additionally,metabolic endotoxemia with altering flora induces a systemic inflammatory response by stimulating the immune system via bacterial translocation.The agenda for diabetes treatment includes the use of short-chain fatty acids,probiotics,prebiotics in the diet,fecal bacteria transplantation,and antibiotics.Animal studies have proven the antidiabetic benefits of numerous bioactive substances,including Flavonoids,Alkaloids,Saponin,and Allicin.However,further research is required to contribute to the treatment of diabetes.展开更多
Immunogenic Cell Death(ICD)represents a mechanism of enhancing T cell-driven response against tumor cells.The process is enabled by release of damage-associated molecular patterns(DAMPs)and cytokines by dying cells.Ba...Immunogenic Cell Death(ICD)represents a mechanism of enhancing T cell-driven response against tumor cells.The process is enabled by release of damage-associated molecular patterns(DAMPs)and cytokines by dying cells.Based on molecular studies and clinical marker assessment,ICD can be a new target for cancer chemotherapy hitherto restricted to a few conventional anticancer drugs.In view of the development of small molecules in targeted cancer therapy,we reported the preliminary evidence on the role of the natural product lepadin A(1)as a novel ICD inducer.Here we describe the ICD mechanism of lepadin A(1)by proving the translocation of the protein calreticulin(CRT)to the plasma membrane of human A2058 melanoma cells.CRT exposure is an ICD marker in clinical studies and was associated with the activation of the intrinsic apoptotic pathway in A2058 cells with lepadin A(1).After the treatment,the tumour cells acquired the ability to activate dendritic cells(DCs)with cytokine release and costimulatory molecule expression that is consistent with a phenotypic profile committed to priming T lymphocytes via a CD91-dependent mechanism.The effect of lepadin A(1)was dose-dependent and comparable to the response of the chemotherapy drug doxorubicin(2),a well-established ICD inducer.展开更多
Although solar exposure is necessary for human health,phototoxicology induced by excessive UVB and UVA radiation,which involves sunburns,skin aging and even tu-morigenesis,has been widely researched.Sunscreen is one o...Although solar exposure is necessary for human health,phototoxicology induced by excessive UVB and UVA radiation,which involves sunburns,skin aging and even tu-morigenesis,has been widely researched.Sunscreen is one of the most important ways to protect skin from UV phototoxic damage.As well as inorganic and organic UV filters,some natural products or plant extracts with aromatic rings in their structures,such as flavonoids or polyphenols,can absorb UV to reduce sunburn,acting as a natu-ral UV filter;they also show antioxidant or/and anti-inflammatory activity.This could explain why,although there are no officially approval natural commercial sun-filters,more and more commercial sunscreen products containing plant extracts are avail-able on the market.Here we summarize articles focusing on natural UV filters from plant published in the last 6 years,selecting the most significant data in order to better understand the photoprotective activity of natural products and extracts from plants,including their major constituents and main biological effects,methods for evaluating UV radiation resistance,anti-UV radiation experimental models and anti-UV radiation mechanisms.展开更多
Over the past several decades,type 2 diabetes mellitus(T2DM)has been considered a global public health concern.Currently,various therapeutic modalities are available for T2DM management,including dietary modifications...Over the past several decades,type 2 diabetes mellitus(T2DM)has been considered a global public health concern.Currently,various therapeutic modalities are available for T2DM management,including dietary modifications,moderate exercise,and use of hypoglycemic agents and lipid-lowering medications.Although the curative effect of most drugs on T2DM is significant,they also exert some adverse side effects.Biologically active substances found in natural medicines are important for T2DM treatment.Several recent studies have reported that active ingredients derived from traditional medicines or foods exert a therapeutic effect on T2DM.This review compiled important articles regarding the therapeutic effects of natural products and their active ingredients on isletβcell function,adipose tissue inflammation,and insulin resistance.Additionally,this review provided an in-depth understanding of the multiple regulatory effects on different targets and signaling pathways of natural medicines in the treatment of T2DM as well as a theoretical basis for clinical effective application.展开更多
The emergence and spread of drug-recalcitrant Plasmodium falciparum parasites threaten to reverse the gains made in the fight against malaria.Urgent measures need to be taken to curb this impending challenge.The highe...The emergence and spread of drug-recalcitrant Plasmodium falciparum parasites threaten to reverse the gains made in the fight against malaria.Urgent measures need to be taken to curb this impending challenge.The higher plant-derived sesquiterpene,quinoline alkaloids,and naphthoquinone natural product classes of compounds have previously served as phenomenal chemical scaffolds from which integral antimalarial drugs were developed.Historical successes serve as an inspiration for the continued investigation of plant-derived natural products compounds in search of novel molecular templates from which new antimalarial drugs could be developed.The aim of this study was to identify potential chemical scaffolds for malaria drug discovery following analysis of historical data on phytochemicals screened in vitro against P.falciparum.To identify these novel scaffolds,we queried an in-house manually curated database of plant-derived natural product compounds and their in vitro biological data.Natural products were assigned to different structural classes using NPClassifier.To identify the most promising chemical scaffolds,we then correlated natural compound class with bioactivity and other data,namely(i)potency,(ii)resistance index,(iii)selectivity index and(iv)physicochemical properties.We used an unbiased scoring system to rank the different natural product classes based on the assessment of their bioactivity data.From this analysis we identified the top-ranked natural product pathway as the alkaloids.The top three ranked super classes identified were(i)pseudoalkaloids,(ii)naphthalenes and(iii)tyrosine alkaloids and the top five ranked classes(i)quassinoids(of super class triterpenoids),(ii)steroidal alkaloids(of super class pseudoalkaloids)(iii)cycloeudesmane sesquiterpenoids(of super class triterpenoids)(iv)isoquinoline alkaloids(of super class tyrosine alkaloids)and(v)naphthoquinones(of super class naphthalenes).Launched chemical space of these identified classes of compounds was,by and large,distinct from that of‘legacy’antimalarial drugs.Our study was able to identify chemical scaffolds with acceptable biological properties that are structurally different from current and previously used antimalarial drugs.These molecules have the potential to be developed into new antimalarial drugs.展开更多
Norepinephrine(NA),a stress hormone,can accelerate hair graying by binding toβ2 adrenergic receptors(β_(2)AR)on melanocyte stem cells(McSCs).From this,NA-β_(2)AR axis could be a potential target for preventing the ...Norepinephrine(NA),a stress hormone,can accelerate hair graying by binding toβ2 adrenergic receptors(β_(2)AR)on melanocyte stem cells(McSCs).From this,NA-β_(2)AR axis could be a potential target for preventing the stress effect.However,identifying selective blockers forβ_(2)AR has been a key challenge.Therefore,in this study,advanced computer-aided drug design(CADD)techniques were harnessed to screen natural molecules,leading to the discovery of rhynchophylline as a promising compound.Rhynchophylline exhibited strong and stable binding within the active site ofβ_(2)AR,as verified by molecular docking and dynamic simulation assays.When administered to cells,rhyncho-phylline effectively inhibited NA-β_(2)AR signaling.This intervention resulted in a significant reduction of hair graying in a stress-induced mouse model,from 28.5%to 8.2%.To gain a deeper understanding of the underlying mechanisms,transcriptome sequencing was employed,which revealed that NA might disrupt melanogenesis by affecting intracellular calcium balance and promoting cell apoptosis.Importantly,rhynchophylline acted as a potent inhibitor of these downstream pathways.In conclusion,the study demonstrated that rhynchophylline has the potential to mitigate the negative impact of NA on melanogenesis by targetingβ_(2)AR,thus offering a promising solution for preventing stress-induced hair graying.展开更多
Since the identified standard genetic code contains 61 triplet codons of three bases for the 20 L-proteinogenic amino acids(AAs),no D-AA should be found in natural products.This is not what is observed in the living w...Since the identified standard genetic code contains 61 triplet codons of three bases for the 20 L-proteinogenic amino acids(AAs),no D-AA should be found in natural products.This is not what is observed in the living world.D-AAs are found in numerous natural compounds produced by bacteria,algae,fungi,or marine animals,and even vertebrates.A review of the literature indicated the existence of at least 132 peptide natural compounds in which D-AAs are an essential part of their structure.All compounds are listed,numbered and described herein.The two biosynthetic routes leading to the presence of D-AA in natural products are:non-ribosomal peptide synthesis(NRPS),and ribosomally synthesized and post-translationally modified peptide(RiPP)synthesis which are described.The methods used to identify the AA chirality within naturally occurring peptides are briefly discussed.The biological activity of an all-L synthetic peptide is most often completely different from that of the D-containing natural compounds.Analyzing the selected natural compounds showed that D-Ala,D-Val,D-Leu and D-Ser are the most commonly encountered D-AAs closely followed by the non-proteinogenic D-allo-Thr.D-Lys and D-Met were the least prevalent D-AAs in natu-rally occurring compounds.展开更多
In the past few decades,acute kidney injury(AKI),characterized by an abrupt decrease in kidney filtration rate,has become a public health issue affecting between 1%and 15%of the population,which causes high morbidity ...In the past few decades,acute kidney injury(AKI),characterized by an abrupt decrease in kidney filtration rate,has become a public health issue affecting between 1%and 15%of the population,which causes high morbidity and death.There is mounting evidence that miRNAs are noncoding single-stranded RNAs with a short length of about 20 nucleotides and have been highly conserved through evolution.Through targeting mRNAs,miRNA may mediate intercellular communication during AKI’s physiological and pathological processes.It is interesting to note that natural products can improve AKI by regulating miRNA expression,which might represent a potentially innovative therapeutic strategy.This review aims at providing an overview of the new data obtained on miRNAs in the treatment and diagnosis of AKI,summarizing studies on natural products improving AKI through regulating miRNAs’expression;in the same time,it will shed new light on AKI risk biomarkers and therapeutic intervention as well.We summarized the roles of miRNAs involved in AKI progression or protection against renal injury in 32 articles;we found five natural products can improve AKI by regulating miRNA expression,which will potentially provide a reference for clinical treatment.Natural products might represent a potentially innovative therapeutic strategy;in the same time,miRNAs will shed new light on AKI risk biomarkers and therapeutic intervention.展开更多
Internal solitary waves(ISWs) contain great energy and have the characteristics of emergency and concealment. To avoid their damage to offshore engineering, a new generation of monitoring and early warning system for ...Internal solitary waves(ISWs) contain great energy and have the characteristics of emergency and concealment. To avoid their damage to offshore engineering, a new generation of monitoring and early warning system for ISWs was developed using technologies of double buoys monitoring, intelligent realtime data transmission, and automatic software identification. The system was applied to the second natural gas hydrates(NGHs) production test in the Shenhu Area, South China Sea(SCS) and successfully provided the early warning of ISWs for 173 days(from October 2019 to April 2020). The abrupt changes in the thrust force of the drilling platform under the attack of ISWs were consistent with the early warning information, proving the reliability of this system. A total of 93 ISWs were detected around the drilling platform. Most of them occurred during the spring tides in October–December 2019 and April 2020, while few of them occurred in winter. As suggested by the theoretical model, the full-depth structure of ISWs was a typical current profile of mode-1, and the velocities of wave-induced currents can reach 80 cm/s and30 cm/s, respectively, in the upper ocean and near the seabed. The ISWs may be primarily generated from the interactions between the topography and semidiurnal tides in the Luzon Strait, and then propagate westward to the drilling platform. This study could serve as an important reference for the early warning of ISWs for offshore engineering construction in the future.展开更多
基金supported by National Natural Science Foundation of China(No.82003775)Talent Project established by Chinese Pharmaceutical Association Hospital Phamacy department.(No.CPA-Z05-ZC-2023-003)+2 种基金Outstanding Young Scholars Foundation of Harbin Medical University Cancer Hospital(No.JCQN2021-04)Heilongjiang Province postdoctoral research fund(No.LBH-Q20050)Special fund for clinical and basic research of medical research development fund(No.YXKY-WS013G).
文摘Reactive oxygen species are closely related to tumor development.In recent years,reactive oxygen species has become a hot spot in tumor therapy,and many natural substances in nature contain compound components with anti-tumor effects.However,there is a lack of discussion on the synergistic anti-tumor effects of natural products in combination with chemotherapeutic drugs through reactive oxygen species.The terms“natural products”,“reactive oxygen species”,“anti-tumor”,and“chemotherapy”were used to identify the synergistic effects of natural products.We conducted a systematic literature search in PubMed and Web of Science databases for relevant research articles and reviews published in recent years.We systematically summarized the studies related to anti-tumor active ingredients in natural compounds in the field of reactive oxygen species in recent years.A total of 77 relevant literatures were included.Among them,45 literatures containing various natural products such as terpenoids,flavonoids,alkaloids,etc.exert anti-tumor effects by regulating reactive oxygen species levels,and 32 literatures regarding adjunctive role of natural products in anti-tumor therapy.In this study,we found that natural products exert anti-tumor effects by elevating reactive oxygen species levels.It provides strong theoretical support for future clinical studies.
基金supported by the National Institutes of Health(R01CA177585,U01CA240346,and R01CA153821)(DY)the Purdue Center for Cancer Research(P30CA023168)+2 种基金the National Natural Science Foundation of China(82173707 and 82322065)the Program for Jiangsu Province Innovative Research Scholar(JSSCRC2021512)the“Double First-Class”University Project(CPUQNJC22_08).
文摘DNA guanine(G)-quadruplexes(G4s)are unique secondary structures formed by two or more stacked Gtetrads in G-rich DNA sequences.These structures have been found to play a crucial role in highly transcribed genes,especially in cancer-related oncogenes,making them attractive targets for cancer therapeutics.Significantly,targeting oncogene promoter G4 structures has emerged as a promising strategy to address the challenge of undruggable and drug-resistant proteins,such as MYC,BCL2,KRAS,and EGFR.Natural products have long been an important source of drug discovery,particularly in the fields of cancer and infectious diseases.Noteworthy progress has recently been made in the discovery of naturally occurring DNA G4-targeting drugs.Numerous DNA G4s,such as MYC-G4,BCL2-G4,KRAS-G4,PDGFR-b-G4,VEGF-G4,and telomeric-G4,have been identified as potential targets of natural products,including berberine,telomestatin,quindoline,sanguinarine,isaindigotone,and many others.Herein,we summarize and evaluate recent advancements in natural and nature-derived DNA G4 binders,focusing on understanding the structural recognition of DNA G4s by small molecules derived from nature.We also discuss the challenges and opportunities associated with developing drugs that target DNA G4s.
基金supported by the National Natural Science Foundation of China(22078281)。
文摘The isolation of minor components from complex natural product matrices presents a significant challenge in the field of purification science due to their low concentrations and the presence of structurally similar compounds.This study introduces an optimized twin-column recycling chromatography method for the efficient and simultaneous purification of these elusive constituents.By introducing water at a small flowing rate between the twin columns,a step solvent gradient is created,by which the leading edge of concentration band would migrate at a slower rate than the trailing edge as it flowing from the upstream to downstream column.Hence,the band broadening is counterbalanced,resulting in an enrichment effect for those minor components in separation process.Herein,two target substances,which showed similar peak position in high performance liquid chromatography(HPLC)and did not exceed 1.8%in crude paclitaxel were selected as target compounds for separation.By using the twin-column recycling chromatography with a step solvent gradient,a successful purification was achieved in getting the two with the purity almost 100%.We suggest this method is suitable for the separation of most components in natural produces,which shows higher precision and recovery rate compared with the common lab-operated separation ways for natural products(thin-layer chromatography and prep-HPLC).
基金supported by the National Natural Science Foundation of China(81873217 and 82074310)the State Key Laboratory of Core Technology in Innovative Chinese Medicine(20221108).
文摘Microcirculatory disturbances are complex processes caused by many factors,including abnormal vasomotor responses,decreased blood flow velocity,vascular endothelial cell injury,altered leukocyte and endothelial cell interactions,plasma albumin leakage,microvascular hemorrhage,and thrombosis.These disturbances involve multiple mechanisms and interactions among mechanisms that can include energy metabolism,the mitochondrial respiratory chain,oxidative stress,inflammatory factors,adhesion molecules,the cytoskeleton,vascular endothelial cells,caveolae,cell junctions,the vascular basement membrane,neutrophils,monocytes,and platelets.In clinical practice,aside from drugs that target abnormal vasomotor responses and platelet adhesion,there continues to be a lack of multi-target drugs that can regulate the complex mechanistic links and interactions underlying microcirculatory disturbances.Natural products have demonstrated obvious positive therapeutic effects in treating ischemia/reperfusion(I/R)-and lipopolysaccharide(LPS)-induced microcirculatory disturbances.In recent years,numerous research papers on the improvement of microcirculatory function by natural products have been published in international journals.In 2008 and 2017,the first listed author of this review was invited to publish reviews in the journal of Pharmacology&Therapeutics on the improvement of microcirculatory disturbances and organ injury induced by I/R using Salvia miltiorrhiza ingredients and other natural components of compounded Chinese medicine,respectively.This review systematically summarizes the effects,targets of action,and mechanisms of natural products regarding improving I/R-and LPSinduced microcirculatory disturbances and tissue injury.Based on this summary,scientific proposals are suggested for the discovery of new drugs to improve microcirculatory disturbances in disease.
基金supported by the Shandong Province Special Fund ‘Frontier Technology and Free Exploration’ from Laoshan Laboratory (No. 8-01)the National Natural Science Foundation of China (No. 42376116)+3 种基金the Special Funds of Shandong Province for Qingdao National Laboratory of Marine Science and Technology (No. 2022QN LM030003)the State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University (No. CMEMR2023-B16)the National Key Research and Development Program of China (No. 2022YFC2601305)the Innovation Center for Academicians of Hainan Province, and the Fundamental Research Funds for the Central Universities (No. 202461059)
文摘Marine natural products(MNPs)are valuable resources for drug development.To date,17 drugs from marine sources are in clinical use,and 33 pharmaceutical compounds are in clinical trials.Presently the success of drug development from the marine resources is higher than the industry average.It is a feasible strategy to conduct the discovery of druglead compounds based on marine chemical ecology by fully exploiting the pharmacological potential of marine chemical defense matters.In the search for bioactive MNPs,our group has constructed a biological resources library including more than 1500 strains of fungi.Focusing on the strategy of Blue Drug Library,we have discovered a series of novel MNPs with abundant biological functions.Highly efficient and scalable total synthesis of(+)-aniduquinolone A(44)and pesimquinolone I(48)have been completed,which will facilitate access to sufficient quantities of candidates for in vivo pharmacological and toxicological studies.As a nucleoprotein(NP)inhibitor,QLA(75)possesses significant anti-influenza A virus(IAV)activities both in vitro and in vivo.CHNQD-00803(76)is a potent and selective AMP-activated kinase(AMPK)activator that can effectively inhibit metabolic disorders and metabolic dysfunction-associated steatohepatitis(MASH)progression.Moreover,we identified two new candidate molecules with potent anti-hepatocellular carcinoma effects.Particularly,as a natural guanine-nucleotide exchange factors for ADP-ribosylation factor GTPases(Arf-GEFs)inhibitor prodrug,CHNQD-01255(78)is qualified to be developed as a targeted candidate anticancer drug,which may be promising to apply for cancer immunotherapy.Hence,it is evident that MNPs play an important role in drug development.
基金This work was supported by Chongqing Natural Science Foundation General Project(2023NSCQ-MSX1633,CSTB2023NSCQ-MSX0393)Key Scientific and Technological Research Project of Chongqing Municipal Education Commission(KJ202302884457913,KJZD-K202302801)+2 种基金2022 Scientific Research Project of Chongqing Medical and Pharmaceutical College(ygz2022104)Scientific Research and Seedling Breeding Project of Chongqing Medical Biotechnology Association(cmba2022kyym-zkxmQ0003)Chongqing Natural Science Foundation(cstc2021jcyj-msxm3191,cstc2021jcyj-msxm0452),respectively.
文摘Hepatocellular carcinoma(HCC)remains a prevalent and challenging malignancy globally,characterized by its numerous causal factors and generally unfavorable prognosis.In the relentless pursuit of effective treatment modalities,natural products have emerged as a promising and relatively non-toxic alternative,garnering significant interest.The integration of natural products with contemporary medical research has yielded encouraging therapeutic outcomes in the management of HCC.This review offers a comprehensive overview of the causal factors underlying HCC,and the diverse treatment options available,and highlights the advancements made by natural products in anti-HCC research.Particularly,we provide an outline of the various types of natural products,their corresponding nomenclature,target molecules,and mechanisms of action that exhibit anti-HCC activities.Natural products are anticipated to play a pivotal role in future comprehensive treatment plans for liver cancer,potentially offering patients improved survival rates and an enhanced quality of life.
文摘BACKGROUND Type 2 diabetes(T2D)is a metabolic disease of impaired glucose utilization and a major cause of cardiovascular disease(CVD).The pathogenesis of both diseases shares common risk factors and mechanisms,and both are significant contributors to global morbidity and mortality.Supplements of natural products for T2D mellitus(T2DM)and CVD can be seen as a potential preventive and effective therapeutic strategy.AIM To critically evaluate the therapeutic potential of natural products in T2D and coronary artery disease(CAD).METHODS By using specific keywords,we strategically searched the PubMed database.Randomized controlled trials(RCTs)were searched as the primary focus that examined the effect of natural products on glycemic control,oxidative stress,and antioxidant levels.We focused on outcomes such as low blood glucose levels,adjustment on markers of oxidative stress and antioxidants.After screening fulllength papers,we included 9 RCTs in our review that met our inclusion criteria.RESULTS In the literature search on the database,we found that various natural products like plant secondary metabolites play a diverse role in the management of CAD.American ginseng,sesame oil and cocoa flavanols proved effective in lowering blood glucose levels and controlling blood pressure,which are key factors in managing T2DM and CVD.In diabetic patients Melissa officinalis effectively reduce inflammation and shows diabetes prevention.Both fish oil and flaxseed oil reduced insulin levels and inflammatory markers,suggesting benefits for both conditions.The lipid profile and endothelial function were enhanced by Nigella sativa oil and Terminalia chebula,which is significant for the management of cardiovascular risk factors in T2DM.Additionally Bilberry extract also showed promise for improving glycemic control in patients with T2DM.CONCLUSION The high level of antioxidant,anti-inflammatory,and anti-angiogenic properties found in natural products makes them promising therapeutic options for the management of CAD,with the potential benefit of lowering the risk of CAD.
文摘Esophageal cancer(ESC)is a malignant tumor that originates from the mucosal epithelium of the esophagus and is part of the digestive tract.Although the exact pathogenesis of ESC has not been fully elucidated,excessive oxidative stress is an important characteristic that leads to the development of many cancers.Abnormal expression of several proteins and transcription factors contributes to oxidative stress in ESCs,which alters the growth and proliferation of ESCs and promotes their metastasis.Natural compounds,including alkaloids,terpenes,polyphenols,and xanthine compounds,can inhibit reactive oxygen species production in ESCs.These compounds reduce oxidative stress levels and subsequently inhibit the oc-currence and progression of ESC through the regulation of targets and pathways such as the cytokine interleukins 6 and 10,superoxide dismutase,the NF-+ACY-kappa+ADs-B/MAPK pathway,and the mammalian Nrf2/ARE target pathway.Thus,targeting tumor oxidative stress has become a key focus in anti-ESC therapy.This review discusses the potential of Natural products(NPs)for treating ESCs and summarizes the application prospects of oxidative stress as a new target for ESC treatment.The findings of this review provide a reference for drug development targeting ESCs.Nonetheless,further high-quality studies will be necessary to determine the clinical efficacy of these various NPs.
基金China Postdoctoral Science Foundation,Grant/Award Number:2020M681768Natural Science Foundation of Jiangsu Province,Grant/Award Number:BK20200653+1 种基金Fundamental Research Funds for the Central Universities,Grant/Award Number:2021GJZPY15National Natural Science Foundation of China,Grant/Award Number:42106210。
文摘It is important to study the effect of hydrate production on the physical and mechanical properties of low-permeability clayey–silty reservoirs for the largescale exploitation of hydrate reservoirs in the South China Sea.In this study,a multiphysical-field coupling model,combined with actual exploration drilling data and the mechanical experimental data of hydrate cores in the laboratory,was established to investigate the physical and mechanical properties of low-permeability reservoirs with different slope angles during 5-year hydrate production by the depressurization method via a horizontal well.The result shows that the permeability of reservoirs severely affects gas production rate,and the maximum gas production amount of a 20-m-long horizontal well can reach186.8 m3/day during the 5-year hydrate production.Reservoirs with smaller slope angles show higher gas production rates.The depressurization propagation and hydrate dissociation mainly develop along the direction parallel to the slope.Besides,the mean effective stress of reservoirs is concentrated in the near-wellbore area with the on-going hydrate production,and gradually decreases with the increase of the slope angle.Different from the effective stress distribution law,the total reservoir settlement amount first decreases and then increases with the increase of the slope angle.The maximum settlement of reservoirs with a 0°slope angle is up to 3.4 m,and the displacement in the near-wellbore area is as high as2.2 m after 5 years of hydrate production.It is concluded that the pore pressure drop region of low-permeability reservoirs in the South China Sea is limited,and various slope angles further lead to differences in effective stress and strain of reservoirs during hydrate production,resulting in severe uneven settlement of reservoirs.
基金This work was supported by the National Key R&D Program of China(2018YFA0903300)the Natural Science Foundation of Tianjin Province(19JCYBJC24200)the National Natural Science Foundation of China(81502966).
文摘Streptomyces is an important treasure trove for natural products discovery.In recent years,many scientists focused on the genetic modification and metabolic regulation of Streptomyces to obtain diverse bioactive compounds with high yields.This review summarized the commonly used regulatory strategies for natural products discovery and overproduction in Streptomyces from three main aspects,including regulator-related strategies,promoter engineering,as well as other strategies employing transposons,signal factors,or feedback regulations.It is expected that the metabolic regulation network of Streptomyces will be elucidated more comprehensively to shed light on natural products research in the future.
文摘Liver cancer is a severe concern for public health officials since the clinical cases are increasing each year,with an estimated 5-year survival rate of 30%–35%after diagnosis.Hepatocellular carcinoma(HCC)constitutes a significant subtype of liver cancer(approximate75%)and is considered primary liver cancer.Treatment for liver cancer mainly depends on the stage of its progression,where surgery including,hepatectomy and liver transplantation,and ablation and radiotherapy are the prime choice.For advanced liver cancer,various drugs and immunotherapy are used as first-line treatment,whereas second-line treatment includes chemotherapeutic drugs from natural and synthetic origins.Sorafenib and lenvatinib are first-line therapies,while regorafenib and ramucirumab are secondline therapy.Various metabolic and signaling pathways such as Notch,JAK/STAT,Hippo,TGF-β,and Wnt have played a critical role during HCC progression.Dysbiosis has also been implicated in liver cancer.Drug-induced toxicity is a key obstacle in the treatment of liver cancer,necessitating the development of effective and safe medications,with natural compounds such as resveratrol,curcumin,diallyl sulfide,and others emerging as promising anticancer agents.This review highlights the current status of liver cancer research,signaling pathways,therapeutic targets,current treatment strategies and the chemopreventive role of various natural products in managing liver cancer.
文摘Diabetes mellitus(DM)is a complicated,globally expanding disease that is influenced by hereditary and environmental variables.Changes in modern society’s food choices,physical inactivity,and obesity are significant factors in the development of type 2 DM(T2DM).The association between changes in intestinal flora and numerous disorders,including obesity,diabetes,and cardiovascular diseases,has been studied in recent years.The purpose of this review is to analyze the mechanisms underlying the alteration of the diabetic patients’intestinal flora,as well as their therapeutic choices.Also included is a summary of the antidiabetic benefits of natural compounds demonstrated by studies.The short-chain fatty acids theory,the bile acid theory,and the endotoxin theory are all potential methods by which intestinal flora contributes to the establishment and progression of T2DM.Due to an intestinal flora imbalance,abnormalities in shortchain fatty acids and secondary bile acids have been found in diabetic patients.Additionally,metabolic endotoxemia with altering flora induces a systemic inflammatory response by stimulating the immune system via bacterial translocation.The agenda for diabetes treatment includes the use of short-chain fatty acids,probiotics,prebiotics in the diet,fecal bacteria transplantation,and antibiotics.Animal studies have proven the antidiabetic benefits of numerous bioactive substances,including Flavonoids,Alkaloids,Saponin,and Allicin.However,further research is required to contribute to the treatment of diabetes.
基金the project“Antitumor Drugs and Vaccines from the Sea(ADViSE)”(B43D18000240007)the FISR COVID Project(B53C22003560002)funded by POR Campania FESR 2014-2020.
文摘Immunogenic Cell Death(ICD)represents a mechanism of enhancing T cell-driven response against tumor cells.The process is enabled by release of damage-associated molecular patterns(DAMPs)and cytokines by dying cells.Based on molecular studies and clinical marker assessment,ICD can be a new target for cancer chemotherapy hitherto restricted to a few conventional anticancer drugs.In view of the development of small molecules in targeted cancer therapy,we reported the preliminary evidence on the role of the natural product lepadin A(1)as a novel ICD inducer.Here we describe the ICD mechanism of lepadin A(1)by proving the translocation of the protein calreticulin(CRT)to the plasma membrane of human A2058 melanoma cells.CRT exposure is an ICD marker in clinical studies and was associated with the activation of the intrinsic apoptotic pathway in A2058 cells with lepadin A(1).After the treatment,the tumour cells acquired the ability to activate dendritic cells(DCs)with cytokine release and costimulatory molecule expression that is consistent with a phenotypic profile committed to priming T lymphocytes via a CD91-dependent mechanism.The effect of lepadin A(1)was dose-dependent and comparable to the response of the chemotherapy drug doxorubicin(2),a well-established ICD inducer.
基金supported by Henan Provincial Department of Education(No.21B350001)Zhengzhou science and technology department(No.ZZSZX202109 and ZZSZX202108).
文摘Although solar exposure is necessary for human health,phototoxicology induced by excessive UVB and UVA radiation,which involves sunburns,skin aging and even tu-morigenesis,has been widely researched.Sunscreen is one of the most important ways to protect skin from UV phototoxic damage.As well as inorganic and organic UV filters,some natural products or plant extracts with aromatic rings in their structures,such as flavonoids or polyphenols,can absorb UV to reduce sunburn,acting as a natu-ral UV filter;they also show antioxidant or/and anti-inflammatory activity.This could explain why,although there are no officially approval natural commercial sun-filters,more and more commercial sunscreen products containing plant extracts are avail-able on the market.Here we summarize articles focusing on natural UV filters from plant published in the last 6 years,selecting the most significant data in order to better understand the photoprotective activity of natural products and extracts from plants,including their major constituents and main biological effects,methods for evaluating UV radiation resistance,anti-UV radiation experimental models and anti-UV radiation mechanisms.
基金Supported by the Nature Science Foundation of Hubei Province,No.2023AFB839.
文摘Over the past several decades,type 2 diabetes mellitus(T2DM)has been considered a global public health concern.Currently,various therapeutic modalities are available for T2DM management,including dietary modifications,moderate exercise,and use of hypoglycemic agents and lipid-lowering medications.Although the curative effect of most drugs on T2DM is significant,they also exert some adverse side effects.Biologically active substances found in natural medicines are important for T2DM treatment.Several recent studies have reported that active ingredients derived from traditional medicines or foods exert a therapeutic effect on T2DM.This review compiled important articles regarding the therapeutic effects of natural products and their active ingredients on isletβcell function,adipose tissue inflammation,and insulin resistance.Additionally,this review provided an in-depth understanding of the multiple regulatory effects on different targets and signaling pathways of natural medicines in the treatment of T2DM as well as a theoretical basis for clinical effective application.
文摘The emergence and spread of drug-recalcitrant Plasmodium falciparum parasites threaten to reverse the gains made in the fight against malaria.Urgent measures need to be taken to curb this impending challenge.The higher plant-derived sesquiterpene,quinoline alkaloids,and naphthoquinone natural product classes of compounds have previously served as phenomenal chemical scaffolds from which integral antimalarial drugs were developed.Historical successes serve as an inspiration for the continued investigation of plant-derived natural products compounds in search of novel molecular templates from which new antimalarial drugs could be developed.The aim of this study was to identify potential chemical scaffolds for malaria drug discovery following analysis of historical data on phytochemicals screened in vitro against P.falciparum.To identify these novel scaffolds,we queried an in-house manually curated database of plant-derived natural product compounds and their in vitro biological data.Natural products were assigned to different structural classes using NPClassifier.To identify the most promising chemical scaffolds,we then correlated natural compound class with bioactivity and other data,namely(i)potency,(ii)resistance index,(iii)selectivity index and(iv)physicochemical properties.We used an unbiased scoring system to rank the different natural product classes based on the assessment of their bioactivity data.From this analysis we identified the top-ranked natural product pathway as the alkaloids.The top three ranked super classes identified were(i)pseudoalkaloids,(ii)naphthalenes and(iii)tyrosine alkaloids and the top five ranked classes(i)quassinoids(of super class triterpenoids),(ii)steroidal alkaloids(of super class pseudoalkaloids)(iii)cycloeudesmane sesquiterpenoids(of super class triterpenoids)(iv)isoquinoline alkaloids(of super class tyrosine alkaloids)and(v)naphthoquinones(of super class naphthalenes).Launched chemical space of these identified classes of compounds was,by and large,distinct from that of‘legacy’antimalarial drugs.Our study was able to identify chemical scaffolds with acceptable biological properties that are structurally different from current and previously used antimalarial drugs.These molecules have the potential to be developed into new antimalarial drugs.
基金the Shenzhen Science and Technology Innovation Committee(grant numbers JCYJ20200109142444449,JCYJ20210324120007021)the National Natural Science Foundation of China(grant numbers 31801196)Basic and Applied Basic Research Foundation of Guangdong Province(grant numbers 2022A1515110645).
文摘Norepinephrine(NA),a stress hormone,can accelerate hair graying by binding toβ2 adrenergic receptors(β_(2)AR)on melanocyte stem cells(McSCs).From this,NA-β_(2)AR axis could be a potential target for preventing the stress effect.However,identifying selective blockers forβ_(2)AR has been a key challenge.Therefore,in this study,advanced computer-aided drug design(CADD)techniques were harnessed to screen natural molecules,leading to the discovery of rhynchophylline as a promising compound.Rhynchophylline exhibited strong and stable binding within the active site ofβ_(2)AR,as verified by molecular docking and dynamic simulation assays.When administered to cells,rhyncho-phylline effectively inhibited NA-β_(2)AR signaling.This intervention resulted in a significant reduction of hair graying in a stress-induced mouse model,from 28.5%to 8.2%.To gain a deeper understanding of the underlying mechanisms,transcriptome sequencing was employed,which revealed that NA might disrupt melanogenesis by affecting intracellular calcium balance and promoting cell apoptosis.Importantly,rhynchophylline acted as a potent inhibitor of these downstream pathways.In conclusion,the study demonstrated that rhynchophylline has the potential to mitigate the negative impact of NA on melanogenesis by targetingβ_(2)AR,thus offering a promising solution for preventing stress-induced hair graying.
文摘Since the identified standard genetic code contains 61 triplet codons of three bases for the 20 L-proteinogenic amino acids(AAs),no D-AA should be found in natural products.This is not what is observed in the living world.D-AAs are found in numerous natural compounds produced by bacteria,algae,fungi,or marine animals,and even vertebrates.A review of the literature indicated the existence of at least 132 peptide natural compounds in which D-AAs are an essential part of their structure.All compounds are listed,numbered and described herein.The two biosynthetic routes leading to the presence of D-AA in natural products are:non-ribosomal peptide synthesis(NRPS),and ribosomally synthesized and post-translationally modified peptide(RiPP)synthesis which are described.The methods used to identify the AA chirality within naturally occurring peptides are briefly discussed.The biological activity of an all-L synthetic peptide is most often completely different from that of the D-containing natural compounds.Analyzing the selected natural compounds showed that D-Ala,D-Val,D-Leu and D-Ser are the most commonly encountered D-AAs closely followed by the non-proteinogenic D-allo-Thr.D-Lys and D-Met were the least prevalent D-AAs in natu-rally occurring compounds.
文摘In the past few decades,acute kidney injury(AKI),characterized by an abrupt decrease in kidney filtration rate,has become a public health issue affecting between 1%and 15%of the population,which causes high morbidity and death.There is mounting evidence that miRNAs are noncoding single-stranded RNAs with a short length of about 20 nucleotides and have been highly conserved through evolution.Through targeting mRNAs,miRNA may mediate intercellular communication during AKI’s physiological and pathological processes.It is interesting to note that natural products can improve AKI by regulating miRNA expression,which might represent a potentially innovative therapeutic strategy.This review aims at providing an overview of the new data obtained on miRNAs in the treatment and diagnosis of AKI,summarizing studies on natural products improving AKI through regulating miRNAs’expression;in the same time,it will shed new light on AKI risk biomarkers and therapeutic intervention as well.We summarized the roles of miRNAs involved in AKI progression or protection against renal injury in 32 articles;we found five natural products can improve AKI by regulating miRNA expression,which will potentially provide a reference for clinical treatment.Natural products might represent a potentially innovative therapeutic strategy;in the same time,miRNAs will shed new light on AKI risk biomarkers and therapeutic intervention.
基金funded by the Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) (GML2019ZD0307)the Marine Geological Survey Program of China Geological Survey (DD20190218, DD20221706)+1 种基金the Key Program of Marine Economy Development Special Foundation of Department of Natural Resources of Guangdong Province (GDNRC [2020] 043)the National Natural Science Foundation of China (41806074, 41730528)。
文摘Internal solitary waves(ISWs) contain great energy and have the characteristics of emergency and concealment. To avoid their damage to offshore engineering, a new generation of monitoring and early warning system for ISWs was developed using technologies of double buoys monitoring, intelligent realtime data transmission, and automatic software identification. The system was applied to the second natural gas hydrates(NGHs) production test in the Shenhu Area, South China Sea(SCS) and successfully provided the early warning of ISWs for 173 days(from October 2019 to April 2020). The abrupt changes in the thrust force of the drilling platform under the attack of ISWs were consistent with the early warning information, proving the reliability of this system. A total of 93 ISWs were detected around the drilling platform. Most of them occurred during the spring tides in October–December 2019 and April 2020, while few of them occurred in winter. As suggested by the theoretical model, the full-depth structure of ISWs was a typical current profile of mode-1, and the velocities of wave-induced currents can reach 80 cm/s and30 cm/s, respectively, in the upper ocean and near the seabed. The ISWs may be primarily generated from the interactions between the topography and semidiurnal tides in the Luzon Strait, and then propagate westward to the drilling platform. This study could serve as an important reference for the early warning of ISWs for offshore engineering construction in the future.