Adsorption,in vitro digestion and human gut microbiota regulation characteristics of three Poria cocos polysaccharides

Poria cocos(PC)is a famous traditional Chinese medicine(TCM)and a widely used healthcare ingredient,which has antiobesity,enhancing immunity and improving sleep effects.Traditionally,only water-soluble poria polysaccharide(WSP)is extracted and applied for clinical application,while insoluble polysaccharide(alkali-soluble poria polysaccharide,ASP)is discarded as herb residue.However,the whole PC has also been historically utilized as functional herbal food.Considering the beneficial role of dietary fiber and the traditional use of PC,ASP may also contribute substantially to the therapy function of PC.Compared to WSP,little attention has been paid to ASP and ASP modified product carboxymethyl poria polysaccharide(CMP)which has been used as an antitumor adjuvant drug.In this study,the oil,cholesterol,metal ions and polyphenols adsorption ability,in vitro simulated digestive and the gut microbiota fermentation characteristics of WSP,ASP and CMP were studied to evaluate the functional values of three P.cocos polysaccharides(PCPs).The results showed that all three PCPs had good adsorption capacity on cholesterol,polyphenols and metal ions(Cd^(2+)/Zn^(2+)/Mg^(2+)),among which ASP showed the highest capacity than WSP and CMP.The adsorption capacity of all three PCPs on heavy metal ions(Cd^(2+)/Zn^(2+))was stronger than that of non-heavy metal ions(Mg^(2+));The in vitro digestibility of all three PCPs was very low,but WSP was slightly higher than ASP and CMP;Moreover,the indigestible residue of all three PCPs could improve the richness and diversity of gut microbiota,among which ASP had the greatest influence.In general,ASP and CMP could significantly promote the proliferation of some probiotics and inhibit the growth of some harmful bacteria.The gut microbiota diversity of CMP was reduced,but the richness of probiotics,especially Parabacteroides distasonis was significantly enhanced compared with the ASP group,and the growth of harmful bacteria Klebsiella pneumoniae was inhibited after CMP treatment.The short-chain fatty acids(SCFAs)analysis results showed that all three PCPs could significantly promote the production of acetic acid,propionic acid and the total acid content compared with blank control group,and SCFAs producing activity was positively correlated with the proliferative capacity of probiotics.Taken together,the good adsorption characteristics and gut microbiota regulatory activity of ASP may lay foundation for its lipid-lowering and immune-improving function.Additionally,the probiotic effect of CMP and ASP indicated that except for only use the water extract of PC in clinic,CMP and ASP also can be used in healthcare to take full advantage of this valuable medicine.

Targeted anti-cancer therapy: Co-delivery of VEGF siRNA and Phenethyl isothiocyanate (PEITC) via cRGD-modified lipid nanoparticles for enhanced anti-angiogenic efficacy

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

Modulation of p75 neurotrophin receptor mitigates brain damage following ischemic stroke in mice

Stroke is a significant leading cause of death and disability in the United States(Tsao et al.,2022).Approximately 87% of strokes fall into the ischemic category,mainly caused by arterial blockage(Jayaraj et al.,2019).Although the only FDA-approved effective medication is tissue plasminogen activator(tPA),it should be administrated within 4.5 hours of ischemic stroke.Furthermore,tPA has been an integral part of managing acute ischemic stro ke.

Mental health status among COVID-19 patients survivors of critical illness in Saudi Arabia:A 6-month follow-up questionnaire study

BACKGROUND Psychological assessment after intensive care unit(ICU)discharge is increasingly used to assess patients'cognitive and psychological well-being.However,few studies have examined those who recovered from coronavirus disease 2019(COVID-19).There is a paucity of data from the Middle East assessing the post-ICU discharge mental health status of patients who had COVID-19.AIM To evaluate anxiety and depression among patients who had severe COVID-19.METHODS This is a prospective single-center follow-up questionnaire-based study of adults who were admitted to the ICU or under ICU consultation for>24 h for COVID-19.Eligible patients were contacted via telephone.The patient’s anxiety and depression six months after ICU discharge were assessed using the Hospital Anxiety and Depression Scale(HADS).The primary outcome was the mean HADS score.The secondary outcomes were risk factors of anxiety and/or depression.RESULTS Patients who were admitted to the ICU because of COVID-19 were screened(n=518).Of these,48 completed the questionnaires.The mean age was 56.3±17.2 years.Thirty patients(62.5%)were male.The main comorbidities were endocrine(n=24,50%)and cardiovascular(n=21,43.8%)diseases.The mean overall HADS score for anxiety and depression at 6 months post-ICU discharge was 11.4(SD±8.5).A HADS score of>7 for anxiety and depression was detected in 15 patients(30%)and 18 patients(36%),respectively.Results from the multivariable ordered logistic regression demonstrated that vasopressor use was associated with the development of anxiety and depression[odds ratio(OR)39.06,95% confidence interval:1.309-1165.8;P<0.05].CONCLUSION Six months after ICU discharge,30% of patients who had COVID-19 demonstrated a HADS score that confirmed anxiety and depression.To compare the psychological status of patients following an ICU admission(with vs without COVID-19),further studies are warranted.

To explore the mechanism of Yigong San anti-gastric cancer and immune regulation

BACKGROUND Yigong San(YGS)is a representative prescription for the treatment of digestive disorders,which has been used in clinic for more than 1000 years.However,the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear.AIM To explore the mechanism of YGS anti-gastric cancer and immune regulation.METHODS Firstly,collect the active ingredients and targets of YGS,and the differentially expressed genes of gastric cancer.Secondly,constructed a protein-protein interaction network between the targets of drugs and diseases,and screened hub genes.Then the clinical relevance,mutation and repair,tumor microenvironment and drug sensitivity of the hub gene were analyzed.Finally,molecular docking was used to verify the binding ability of YGS active ingredient and hub genes.RESULTS Firstly,obtained 55 common targets of gastric cancer and YGS.The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6,EGFR,MMP2,MMP9 and TGFB1 as the hub genes.The 5 hub genes were involved in gastric carcinogenesis,staging,typing and prognosis,and their mutations promote gastric cancer progression.Finally,molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets.CONCLUSION YGS has the effect of anti-gastric cancer and immune regulation.

Interaction of major facilitator superfamily domain containing 2A with the blood-brain barrier

The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly understood.The major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier function.It plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain barrier.Furthermore,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain barrier.This paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier permeability.This comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to date.This will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic monitoring.In addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier leakage in various diseases and the research progress on cross-blood-brain barrier drug delivery are summarized.This review may contribute to the development of new approaches for the treatment of neurological diseases.

Understanding the Novel Approach of Nanoferroptosis for Cancer Therapy

As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer cells.The molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of cells.Due to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active targeting.This review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and metastasis.Additionally,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.

On implications of somatostatin in diabetic retinopathy

Somatostatin,a naturally produced neuroprotective peptide,depresses excitatory neurotransmission and exerts anti-proliferative and anti-inflammatory effects on the retina.In this review,we summarize the progress of somatostatin treatment of diabetic retinopathy through analysis of relevant studies published from February 2019 to February 2023 extracted from the PubMed and Google Scholar databases.Insufficient neuroprotection,which occurs as a consequence of declined expression or dysregulation of retinal somatostatin in the very early stages of diabetic retinopathy,triggers retinal neurovascular unit impairment and microvascular damage.Somatostatin replacement is a promising treatment for retinal neurodegeneration in diabetic retinopathy.Numerous pre-clinical and clinical trials of somatostatin analog treatment for early diabetic retinopathy have been initiated.In one such trial(EUROCONDOR),topical administration of somatostatin was found to exert neuroprotective effects in patients with pre-existing retinal neurodysfunction,but had no impact on the onset of diabetic retinopathy.Overall,we concluded that somatostatin restoration may be especially beneficial for the growing population of patients with early-stage retinopathy.In order to achieve early prevention of diabetic retinopathy initiation,and thereby salvage visual function before the appearance of moderate non-proliferative diabetic retinopathy,several issues need to be addressed.These include the needs to:a)update and standardize the retinal screening scheme to incorporate the detection of early neurodegeneration,b)identify patient subgroups who would benefit from somatostatin analog supplementation,c)elucidate the interactions of somatostatin,particularly exogenously-delivered somatostatin analogs,with other retinal peptides in the context of hyperglycemia,and d)design safe,feasible,low cost,and effective administration routes.

Progress in experimental models to investigate the in vivo and in vitro antidiabetic activity of drugs

Diabetes mellitus is one of the world's most prevalent and complex metabolic disorders,and it is a rapidly growing global public health issue.It is characterized by hyperglycemia,a condition involving a high blood glucose level brought on by deficiencies in insulin secretion,decreased activity of insulin,or both.Prolonged effects of diabetes include cardiovascular problems,retinopathy,neuropathy,nephropathy,and vascular alterations in both macro-and micro-blood vessels.In vivo and in vitro models have always been important for investigating and characterizing disease pathogenesis,identifying targets,and reviewing novel treatment options and medications.Fully understanding these models is crucial for the researchers so this review summarizes the different experimental in vivo and in vitro model options used to study diabetes and its consequences.The most popular in vivo studies involves the small animal models,such as rodent models,chemically induced diabetogens like streptozotocin and alloxan,and the possibility of deleting or overexpressing a specific gene by knockout and transgenic technologies on these animals.Other models include virally induced models,diet/nutrition induced diabetic animals,surgically induced models or pancreatectomy models,and non-obese models.Large animals or non-rodent models like porcine(pig),canine(dog),nonhuman primate,and Zebrafish models are also outlined.The in vitro models discussed are murine and human beta-cell lines and pancreatic islets,human stem cells,and organoid cultures.The other enzymatic in vitro tests to assess diabetes include assay of amylase inhibition and inhibition ofα-glucosidase activity.

Current perspective on amyloid aggregation accelerating properties of the artificial butter flavoring,diacetyl

The amyloid—what peptide can resist its entropic bliss?Without kinetic barricades and chaperones,most peptides would simply tumble down that precipice.The amyloid-β(Aβ) peptides are understood to underlie the hallmark pathology of Alzheimer's disease(AD) and are considered one of the causative factors for neurodegeneration and cognitive impairment.AD affects critical connected structures within the brain that are responsible for memory,language,and social behavior.

Structural characterization and prebiotic potential of polysaccharides from Polygonatum sibiricum

Polygonatum sibiricum has been widely used due to its excellent biological activities.We prepared a novel polysaccharide from P.sibiricum(PSP)in this study.According a monosaccharide composition analysis,PSP was mainly composed of fructose and glucose with a molar percentage of 93.81:5.12.The main linkage types were identified asα-D-Glcp-1→and→2-β-D-Fruf-1→.The molecular weight of PSP showed no significant change after simulated salivary and gastrointestinal digestion.However,PSP could be broken down by intestinal bacteria.Our findings revealed that PSP administration increased the abundance of probiotics such as Bifidobacterium.Furthermore,the results showed that gut microbes could utilize PSP to produce short-chain fatty acids including acetic acid,propionic acid,and butyric acid.Also,the PSP fermentation broth displayed an excellent scavenging effect on free radicals,including 2,2-diphenyl-1-picrylhydrazyl radical,superoxide radical,and hydroxyl radical.In summary,this study will help to promote the application of PSP as prebiotics in functional food and the medical industry.

Unveiling osteoprotective potential of biologically active naringenin in rats with dexamethasone-induced osteoporosis

Objective To investigate the protective effects of naringenin(NRG)against dexamethasone(DEX)-induced osteoporosis(OP)in rats.Methods Molecular docking of NRG was done with AutoDock Vina 1.2.0 software.Forty-eight female Wistar rats were randomly divided into six groups(n=8 each):normal control(NC),DEX(7 mg/kg,i.m.),NRG-low(NRG-L;25 mg/kg,i.g.),NRG-medium(NRG-M;50 mg/kg,i.g.),NRG-high(NRG-H;100 mg/kg,i.g.),and alendronate(ALN;0.25 mg/d,i.g.)groups.OP was induced by administering DEX once a week for five weeks in all groups except NC group.Begining in the third week after the initial DEX administration,the rats in NRG-L,NRG-M,NRG-H,and ALN groups received the corresponding treatments daily for three weeks,while NC and DEX groups received no additional treatment.Serum samples were collected at the end of the experiment for biochemical,bone turnover,antioxidant,lipid profile,and inflammatory cytokine analyses.Femur bones underwent physical parameter testing and histopathological examination.Results The molecular docking results illustrated that NRG docked with calcitonin(CT),lowdensity lipoprotein(LDL),bone morphogenetic protein(BMP),vascular endothelial growth factor(VEGF)receptor,forkhead transcription factors,and osteoprogenitor cells showed good binding energy.In rats administered with 25,50,and 100 mg/kg NRG,there was a significant enhancement in serum biochemical indices,characterized by a reduction in tartrate-resistant acid phosphatase(TRAP),parathyroid hormone(PTH),and an elevation in osteocalcin(OC)and CT levels(P<0.05,P<0.01,and P<0.001,respectively).Despite no significant changes in thickness,weight,and length(P>0.05),there was a marked increase in bone mineral density(BMD)(P<0.01,P<0.001,and P<0.001,respectively).Antioxidant enzyme markers showed significant upregulation,with higher glutathione,superoxide dismutase,and catalase,and a concurrent decrease in malondialdehyde(MDA)(P<0.05,P<0.01,and P<0.001,respectively).The lipid profile also improved significantly,with lower cholesterol(CH),triglycerides(TG),and low-density lipoprotein(LDL)levels,and an increase in high-density lipoprotein(HDL)level(P<0.05,P<0.01,and P<0.001,respectively).Inflammatory cytokine levels were reduced,as evidenced by decreases in tumor necrosis factor(TNF),interleukin(IL)-6,and IL-1β(P<0.05,P<0.01,and P<0.001,respectively).Furthermore,histological alterations revealed obvious improvements,and the body weight of rats treated with NRG showed an increase compared with DEX group.Conclusion These findings imply that NRG exhibited a protective effect against DEX-induced OP in rats as it promotes the bone formation process by increasing the number of bone turnover markers including OC and CT,and restoring of antioxidant status,lipid metabolism,and inflammatory markers.

Comparative study of the effects of Tartary buckwheat seed and sprout consumption on the physiological indices and gut microbiota of C57BL/6J mice

Tartary buckwheat(Fagopyrum tataricum)is a well-known pseudocereal for its health and economic value.However,abundant antinutritional factors(ANFs)reduces its health benefits.As reported,germination can improve the nutritional profile of grains.In this study,we systematically evaluate the safety of Tartary buckwheat seeds(TB)and Tartary buckwheat sprouts(TBS)used as high active ingredients.After evaluating nutrition levels,bioactive compounds and ANFs in TBS during germinating,5^(th)-day TBS were selected as the raw material.C57BL/6J mice were gavaged daily with distilled water,TB,or TBS for 6 weeks.The physiological indices related to ANFs were determined.Results showed that the TB intake tends to generate negative effects on the gut microbiota,and organs.Additionally,upon TB intake,the Fe^(3+)content in serum,trypsin activity in pancreas and jejunum decreased,while the cytokine,IgE,and histamine levels in serum,water content in faeces,cytokine levels in liver and jejunum increased.Conversely,TBS did not induce any obvious negative effects on the above relevant indices and showed better lipid-lowering effect.Altogether,TBS are safer and more effective as a raw material to produce the functional food for long-term consumption with the intention of preventing and treating hyperlipidaemia.

Gut microbiome-based thiamine metabolism contributes to the protective effect of one acidic polysaccharide from Selaginella uncinata(Desv.)Spring against inflammatory bowel disease

Inflammatory bowel disease(IBD)is a serious disorder,and exploration of active compounds to treat it is necessary.An acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata(Desv.)Spring,which contained galacturonic acid,galactose,xylose,arabinose,and rhamnose with the main chain structure of→4)-α-d-GalAp-(1→and→6)-β-d-Galp-(1→and the branched structure of→5)-α-l-Araf-(1→.Animal experiments showed that compared with Model group,SUSP-4 significantly improved body weight status,disease activity index(DAI),colonic shortening,and histopathological damage,and elevated occludin and zonula occludens protein 1(ZO-1)expression in mice induced by dextran sulfate sodium salt(DSS).16S ribosomal RNA(rRNA)sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and Alistipes.Metabolomics results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism,which was further confirmed by a targeted metabolism study.Fecal transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice.A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B(p-NF-κB)and cyclooxygenase-2(COX-2)and elevating NF-E2-related factor 2(Nrf2)levels compared with Model group.In conclusion,SUSP-4 affected thiamine metabolism by regulating Akkermania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against IBD.This is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD,showing great potential for in-depth research and development applications.

Ganoderma lucidum:a comprehensive review of phytochemistry,efficacy,safety and clinical study

Ganoderma lucidum,one of the most well-known edible fungi,is believed to be very beneficial for longevity and vitality.A long usage history suggests that G.lucidum has various clinical therapeutic effects.And experimental studies have confirmed that G.lucidum has multiple pharmacological effects,including antitumor,anti-microbial,anti-HIV protease,and antidiabetic activity and so on.With the deepening of research,more than 300 compounds have been isolated from G.lucidum.There is an increasing population of G.lucidum-based products,and its international development is expanding.Currently,G.lucidum has drawn much attention to its chemical composition,therapeutic effect,clinical value,and safety.This paper provides a comprehensive review of these aspects to enhance the global promotion of G.lucidum.

The effect of celastrol in combination with 5-fluorouracil on proliferation and apoptosis of gastric cancer cell lines

Background:Despite the availability of chemotherapy drugs such as 5-fluorouracil(5-FU),the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side effects.This study aimed to investigate the effect of celastrol in combination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines(AGS and EPG85-257).Materials and Methods:In this in vitro study,AGS and EPG85-257 cells were treated with different concentrations of celastrol,5-FU,and their combination.Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)assay.The synergistic effect of 5-FU and celastrol was studied using Compusyn software.The DNA content at different phases of the cell cycle and apoptosis rate was measured usingflow cytometry.Results:Co-treatment with low concentrations(10%inhibitory concentration(IC10))of celastrol and 5-FU significantly reduced IC50(p<0.05)so that 48 h after treatment,IC50 was calculated at 3.77 and 6.9μM for celastrol,20.7 and 11.6μM for 5-FU,and 5.03 and 4.57μM for their combination for AGS and EPG85-257 cells,respectively.The mean percentage of apoptosis for AGS cells treated with celastrol,5-FU,and their combination was obtained 23.9,41.2,and 61.9,and for EPG85-257 cells 5.65,46.9,and 55.7,respectively.In addition,the 5-FU and celastrol-5-FU combination induced cell cycle arrest in the synthesis phase.Conclusions:Although celastrol could decrease the concentration of 5-fluorouracil that sufficed to suppress gastric cancer cells,additional studies are required to arrive at conclusive evidence on the anticancer effects of celastrol.

Eco-friendly high-throughput screening of cephalosporins impurities: Utilizing 2D-carbon microfiber fractionation system combined with quadrupole time of flight high-resolution mass spectrometer

Owing to its high sensitivity,selectivity,and accuracy,liquid chromatography coupled with mass spectrometry(LC-MS)is commonly employed to screen,confirm,and quantify impurities in drugs[1].However,LC-MS has certain drawbacks such as complicated pretreatment steps,long analysis time,large consumption of organic solvents,high maintenance costs,and,most notably,the need for high-pressure pumps and compatible hardware because of the high column backpressure[2].In this study,a two-dimensional(2D)microscale carbon fiber(CF)/active carbon fiber(ACF)system combined with a quadrupole time-of-flight high-resolution mass spectrometry(2DmCFs-QTOF-HRMS)system was developed to rapid screening impurities in the typical three generations of oral cephalosporins,i.e.,cephalexin tablets(CPXTs),cefuroxime axetil tablets(CFATs),and cefixime tablets(CFXTs)(Fig.S1).The“fuzzy chromatographic separation”sample pretreatment method separates complex samples into high-,medium-,and weak-polar fractions for successive detection of MS,achieving effective reduction of the ion suppression effect in electrospray ionization(ESI)-MS and improving the MS detection sensitivity.Compared to high performance liquid chromatography(HPLC)-MS,this method has distinct advantages such as less organic solvent consumption(1.5 mL),shorter separation and analysis times(5 min),more information on impurities,and high reproducibility.

Material basis and pharmacodynamic mechanism of YangshenDingzhi granules in the intervention of viral pneumonia:Based on serum pharmacochemistry and network pharmacology

Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology.Methods:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection of blood component-related targets and disease-related targets was determined using Venny 2.1.Protein-protein interaction networks were constructed using the STRING database.The Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway networks.Further,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia.Results:Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum.Among these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant roles.In vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 replicon.Further,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1.Conclusion:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.

Effects of Inoculation with Phosphate Solubilizing Bacteria on the Physiology,Biochemistry,and Expression of Genes Related to the Protective Enzyme System of Fritillaria taipaiensis P.Y.Li

Fritillaria taipaiensis P.Y.Li is a widely used medicinal herb in treating pulmonary diseases.In recent years,its wild resources have become scarce,and the demand for efficient artificial cultivation has significantly increased.This article is the first to apply phosphate solubilizing bacteria isolated from the rhizosphere soil of F.taipaiensis P.Y.Li to the cultivation process of F.taipaiensis P.Y.Li.The aim is to identify suitable reference strains for the artificial cultivation and industrial development of F.taipaiensis P.Y.Li by examining the effects of various phosphate solubilizing bacteria and their combinations on photosynthesis,physiological and biochemical properties,and gene expression related to the protective enzyme system in F.taipaiensis P.Y.Li.The experiment,conducted in pots at room temperature,included a control group(CK)and groups inoculated with inorganic phosphorussolubilizing bacteria:W1(Bacillus cereus),W2(Serratia plymuthica),W12(Bacillus cereus and Serratia plymuthica),and groups inoculated with organophosphorus-solubilizing bacteria:Y1(Bacillus cereus),Y2(Bacillus cereus),Y12(Bacillus cereus and Bacillus cereus),totaling seven groups.Compared to CK,most growth indices in the bacterial addition groups showed significant differences,with W12 achieving the highest values in all indices except the leaf area index.The content of photosynthetic pigments,photosynthetic parameters,and osmoregulatory substances increased variably in each bacterial treatment group.W12 exhibited the highest content of chlorophyll a and soluble protein,while W1 had the highest free proline content.The activities of peroxidase(POD),superoxide dismutase(SOD),and catalase(CAT)in all inoculated groups were higher than in CK,with significant changes in SOD and CAT activities.The malondialdehyde(MDA)content in all inoculated groups was lower than in CK,with Y12 being the lowest,at approximately 30%of CK.Gene expression corresponding to these three enzymes also increased variably,with POD expression in Y2 being the highest at 2.73 times that of CK.SOD and CAT expression in Y12 were the highest,at 1.84 and 4.39 times that of CK,respectively.These results indicate that inoculating phosphate solubilizing bacteria can enhance the growth of F.taipaiensis P.Y.Li,with the mixed inoculation groups W12 and Y12 demonstrating superior effects.This lays a theoretical foundation for selecting bacterial fertilizers in the cultivation process of F.taipaiensis P.Y.Li.

Mapping COVID-19 in India:Southern states at the forefront of new JN.1 variant

A new variant,JN.1,stemming from the omicron subvariant BA.2.86,garnered the attention of the World Health Organization(WHO)as a"variant of interest."Despite its rapid global spread,especially in the US,Canada,France,Singapore,Sweden[1],and the UK,JN.1 is considered to pose minimal danger.Current vaccinations are believed to remain effective against it.The WHO underscores the importance of maintaining immunization records amid co-occurring respiratory illnesses,and epidemiologists recommend monitoring hospitalizations,particularly in areas with low vaccination rates.