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.

Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

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.

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.

Hepatoprotective effects of Xiaoyao San formula on hepatic steatosis and inflammation via regulating the sex hormones metabolism

BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival.However,the molecular mechanisms underlying that remain unclear.AIM To investigate the role and mechanisms of MXS in ameliorating hepatic injury,steatosis and inflammation.METHODS A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis(NASH)model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes.Liver tissues were collected for western blotting and immunohisto chemistry(IHC)assays.Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining.The serum samples were collected for biochemical assays and NMR-based metabonomics analysis.The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH.RESULTS MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress.The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation,inflammation and hepatic fibrosis in the pathogenesis of NASH.The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis.Mechanistically,we found that MXS protected against NASH by attenuating the sex hormone-related metabolism,especially the metabolism of male hormones.CONCLUSION MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones.Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.

Knee osteoarthritis:A review of animal models and intervention of traditional Chinese medicine

Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same outcome.Consequently,researchers are interested in studying KOA and require appropriate animal models for basic research.Chinese herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget effects.The potential benefits in the treatment of KOA continue to attract attention.Purpose:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal models.This will help researchers make informed decisions when choosing an animal model.Methods:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to 2023.Results:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal models.Conclusion:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.

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.

A study on utilization of anti-asthmatic drugs at a medical college hospital in India

Objective:To study the usage of anti-asthmatic dugs and enumerate the patients’ noncompliance. Methods:The study was conducted from 5th Feb,2006 to 5th Mar,2006.The samples were from the general medicine ward.All patients with respiratory tract infection who received anti-asthmatic drugs were included in the study.Data were collected from clinical notes and structured patient’s data,and patient interview utilizing a piloted questionnaire data collection form.The questionnaire included patient demographics,anti-asthmatics prescribed, dose,frequency and previous treatment if any and its duration,concomitant medications etc. Results:26.31%of patients were 61-70 years old.Among 57 patients,91.23%of patients received multi-therapy,8.77%of patients received mono-therapy,59.65%of patients took over the counter(OTC) drugs and 57.89%of patients were non compliant.Anti-asthmatic drugs were prescribed to asthmatic patients as oral,inhalation and others(injections),and more than one route were used for administration of drugs.Conclusion:The anti-asthmatics are used to treat breathing difficulties such as allergy.Poor compliance to treatment is common among the patients,which makes it difficult to manage asthma and increases both morbidity and mortality.It is suggested that interventions have to be done by providing counseling and improving the current prescribing trend for better and rational utilization.

Emergence of taurine as a therapeutic agent for neurological disorders

Taurine is a sulfur-containing,semi-essential amino acid that occurs naturally in the body.It alternates between inflammation and oxidative stress-mediated injury in various disease models.As part of its limiting functions,taurine also modulates endoplasmic reticulum stress,Ca^(2+)homeostasis,and neuronal activity at the molecular level.Taurine effectively protects against a number of neurological disorders,including stro ke,epilepsy,cerebral ischemia,memory dysfunction,and spinal cord injury.Although various therapies are available,effective management of these disorders remains a global challenge.Approximately 30 million people are affected worldwide.The design of taurine fo rmation co uld lead to potential drugs/supplements for the health maintenance and treatment of central nervous system disorders.The general neuroprotective effects of taurine and the various possible underlying mechanisms are discussed in this review.This article is a good resource for understanding the general effects of taurine on various diseases.Given the strong evidence for the neuropharmacological efficacy of taurine in various experimental paradigms,it is concluded that this molecule should be considered and further investigated as a potential candidate for neurotherapeutics,with emphasis on mechanism and clinical studies to determine efficacy.

Spatially resolved metabolomics visualizes heterogeneous distribution of metabolites in lung tissue and the anti-pulmonary fibrosis effect of Prismatomeris connate extract

Pulmonary fibrosis (PF) is a chronic progressive end-stage lung disease. However, the mechanisms underlying the progression of this disease remain elusive. Presently, clinically employed drugs are scarce for the treatment of PF. Hence, there is an urgent need for developing novel drugs to address such diseases. Our study found for the first time that a natural source of Prismatomeris connata Y. Z. Ruan (Huang Gen, HG) ethyl acetate extract (HG-2) had a significant anti-PF effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic (TGF-β1/Smad) pathway. Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation, cellular response to reactive oxygen species, and extracellular matrix (ECM) disassembly. Moreover, mass spectrometry imaging (MSI) was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-PF metabolic mechanism of HG-2, which was related to arginine biosynthesis and alanine, asparate and glutamate metabolism, the downregulation of arachidonic acid metabolism, and the upregulation of glycerophospholipid metabolism. In conclusion, we elaborated on the relationship between metabolite distribution and the progression of PF, constructed the regulatory metabolic network of HG-2, and discovered the multi-target therapeutic effect of HG-2, which might be conducive to the development of new drugs for PF.

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.

Network pharmacology study and in vitro experimental validation of Xiaojianzhong decoction against gastric cancer

BACKGROUND Cancer is one of the most serious threats to human health worldwide.Conventional treatments such as surgery and chemotherapy are associated with some drawbacks.In recent years,traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians,and has become an indispensable part of the comprehensive treatment for gastric cancer.AIM To investigate the mechanism of Xiaojianzhong decoction(XJZ)in the treatment of gastric cancer(GC)by utilizing network pharmacology and experimental validation,so as to provide a theoretical basis for later experimental research.METHODS We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics.Subsequently,we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8,apoptosis,cell cycle,and clone formation assays.Additionally,we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins.RESULTS XJZ mainly regulates IL6,PTGS2,CCL2,MMP9,MMP2,HMOX1,and other target genes and pathways in cancer to treat GC.The inhibition of cell viability,the increase of apoptosis,the blockage of the cell cycle at the G0/G1 phase,and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment.In addition,XJZ induced a decrease in the mRNA expression of IL6,PTGS2,MMP9,MMP2,and CCL2,and an increase in the mRNA expression of HOMX1.XJZ significantly inhibited the expression of IL6,PTGS2,MMP9,MMP2,and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein.CONCLUSION XJZ exerts therapeutic effects against GC through multiple components,multiple targets,and multiple pathways.Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.

The Managerial Role of Pharmacist at Community Pharmacy Setting in Saudi Arabia

In Saudi Arabia community pharmacies by law, be owned and managed by pharmacists. Although these two functions seemed to be the same but in reality, they are not. Some studies showed that in community pharmacy managerial functions account for more than 50% of total routine and critical activity for all managerial position surveyed while other study showed that only 13.6% of the pharmacist’s time spent in administrative activities. This article addressed the role of the pharmacist as manager and the way in which he/she manages the pharmacy to ensure optimum productivity. The main part of this review discussed the managerial role of pharmacist in management of human resources, financial resources, marketing, inventory, information resources and space management of the pharmacy. Additionally, the management process, professional skills of managers, development of managerial skills, problems in management process and their resolution were also discussed. In addition to management functions which also include planning, organizing, leading, and controlling processes. The author concluded that the skills of pharmacy managers may vary because of the lack of formalized management training programs. To bridges a gap in management education, interested pharmacists should be encouraged to shift their career goals from professional to pharmacy administration. In addition, expansion of curricula in pharmacy management to include management training of highest possible caliber in managerial skills is highly demanded. Formalized management training programs for those involved in community pharmacy practice are also warranted.

Teaching Physical Assessment and Disease Screening to Students in the Health Professions: A Focus in Pharmacy Education

Background: As pharmacists continue to transition into the provision of public health care, physical assessment and disease screening will become part of their everyday practice, in a similar manner that it has been for doctors and nurses. Objective: The aim was to describe the health assessment of undergraduate curricula across three disciplines involved in public health care and to explore the students’ perceived training in a variety of health assessments. Method: Instructors of courses related to health assessment in medicine, nursing, and pharmacy colleges in Qatar were invited to participate in the curriculum review process. Students’ perceived training in a variety of health assessments was assessed using a self-administered survey. Both descriptive and inferential statistics were used to analyze the survey responses. Results: A narrative description for the similarities and differences in the health assessment curricula across the three colleges was provided. Blood pressure, heart rate, and heart sounds were the health assessments that almost all students received training on, although there were differences in where the training was delivered. The health assessments that the students perceived having received least training on were measuring bone mineral density, blood cholesterol and international normalized ratio reported by only 37%, 41% and 44% of students, respectively. Conclusion: The study identified a close alignment between each of the health discipline’s scope of practice and the health assessment content taught in each individual program. It also identified possible curricular gaps towards learning the skills of patient assessment that may need to be addressed.

Network pharmacology and computational analysis of berberine and kuwanon Z as possible natural antiviral compounds in COVID-19

Background:Global efforts to discover effective therapeutic agents for combating coronavirus disease 19(COVID-19)have intensified the exploration of natural compounds with potential antiviral properties.In this study,we utilized network pharmacology and computational analysis to investigate the antiviral effects of Berberine and Kuwanon Z against severe acute respiratory syndrome coronavirus 2,the viruses responsible for COVID-19.Method:Utilizing comprehensive network pharmacology approaches,we elucidated the complex interactions between these compounds and the host biological system,highlighting their multitarget mechanisms.Network pharmacology identifies COVID-19 targets and compounds through integrated protein‒protein interaction and KEGG pathway analyses.Molecular docking simulation studies were performed to assess the binding affinities and structural interactions of Berberine and Kuwanon Z with key viral proteins,shedding light on their potential inhibitory effects on viral replication and entry.Results:Network-based analyses revealed the modulation of crucial pathways involved in the host antiviral response.Compound-target network analysis revealed complex interactions(122 nodes,121 edges),with significant interactions and an average node degree of 1.37.KEGG analysis revealed pathways such as the COVID-19 pathway,chemokines and Jak-sat in COVID-19.Docking studies revealed that Kuwanon Z had binding energies of-10.5 kcal/mol for JAK2 and-8.1 kcal/mol for the main protease.Conclusion:The findings of this study contribute to the understanding of the pharmacological actions of Berberine and Kuwanon Z in the context of COVID-19,providing a basis for further experimental validation.These natural compounds exhibit promise as potential antiviral agents,offering a foundation for the development of novel therapeutic strategies in the ongoing battle against the global pandemic.

Genome Sequencing,Probiotic Analysis,and Oxalate Degradation Modification of Limosilactobacillus reuteri Q35

Limosilactobacillus reuteri is a microbe intricately linked to humans and animal health.A thorough assessment of its safety and potential benefits is imperative prior to its application in human and animals.In this investigation,we performed a comprehensive analysis encompassing genome sequencing,genomic analysis,and phenotypic characterization of L.reuteri Q35,an exceptionally proficient producer of reuterin.The whole genome sequencing results showed that the complete genome sequence spans 2145158 bp with a GC content of 38.9%and encompasses 2121 genes.Initial identification of antibiotic-resistant genes,virulence factors,and toxin-coding genes in the genome substantiated the strain’s low-risk status.Subsequent tests for antibiotic resistance,acute oral toxicology,and hemolysis further confirmed its elevated safety level.The genome of L.reuteri Q35 was found to contain genes associated with adhesion and stress tolerance.Following exposure to artificial gastric juice and bile salt,the strain exhibited a higher survival rate and demonstrated a strong scavenging ability for hydroxyl free radicals in antioxidant capacity tests.These findings suggested that L.reuteri Q35 possesses unique probiotic properties.Additionally,the genome of strain Q35 harbors three truncated oxaloyl-CoA decarboxylase genes(oxc1,oxc2 and oxc3),overexpression of which resulted in a significant increase in ammonium oxalate degradation from 29.5%to 48.8%.These findings highlight that L.reuteri Q35 exhibits both favorable safety characteristics alongside beneficial properties,making it a promising candidate for treating metabolic disorders such as hyperoxaluria.

Mechanisms and therapeutic targets of ferroptosis: Implications for nanomedicine design

Ferroptosis is a nonapoptotic form of cell death and differs considerably from the well-known forms of cell death in terms of cell morphology,genetics,and biochemistry.The three primary pathways for cell ferroptosis are system Xc^(-)/glutathione peroxidase 4(GPX4),lipid metabolism,and ferric metabolism.Since the discovery of ferroptosis,mounting evidence has revealed its critical regulatory role in several diseases,especially as a novel potential target for cancer therapy,thereby attracting increasing attention in the fields of tumor biology and anti-tumor therapy.Accordingly,broad prospects exist for identifying ferroptosis as a potential therapeutic target.In this review,we aimed to systematically summarize the activation and defense mechanisms of ferroptosis,highlight the therapeutic targets,and discuss the design of nanomedicines for ferroptosis regulation.In addition,we opted to present the advantages and disadvantages of current ferroptosis research and provide an optimistic vision of future directions in related fields.Overall,we aim to provide new ideas for further ferroptosis research and inspire new strategies for disease diagnosis and treatment.

Electrostatic spraying for fine-tuning particle dimensions to enhance oral bioavailability of poorly water-soluble drugs

While spray-drying has been widely utilized to improve the bioavailability of poorly water-soluble drugs,the outcomes often exhibit suboptimal particle size distribution and large particle sizes,limiting their effectiveness.In this study,we introduce electrostatic spraying as an advanced technology tailored for poorly water-soluble drugs,enabling the fabrication of nanoparticles with fine and uniform particle size distribution.Regorafenib(1 g),as a model drug,copovidone(5 g),and sodium dodecyl sulfate(0.1 g)were dissolved in 200 ml ethanol and subjected to conventional-spray-dryer and electrostatic spray dryer.The electrostatic spray-dried nanoparticles(ESDN)showed smaller particle sizes with better uniformity compared to conventional spray-dried nanoparticles(CSDN).ESDN demonstrated significantly enhanced solubility and rapid release in water.In vitro studies revealed that ESDN induced apoptosis in HCT-116 cells to a greater extent,exhibiting superior cytotoxicity compared to CSDN.Furthermore,ESDN substantially improved oral bioavailability and antitumor efficacy compared to CSDN.These findings suggest that ESD shows potential in developing enhanced drug delivery systems for poorly water-soluble drugs,effectively addressing the limitations associated with CSD methods.

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.