Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Isc...Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Ischemic retinopathy can be acute,such as in central or branch retinal artery occlusion,or chronic,such as with DR(Figure 1).Although the causes of retinopathies are diverse,one pathogenic event shared by these conditions is the myeloid cell response to retinal ischemia(Shahror et al.,2024a).展开更多
To measure the experiences, knowledge and attitudes of community pharmacists in Jordan towards diabetes and its management. The validated diabetes knowledge survey tool obtained from Simpson et al, 2009 was modified t...To measure the experiences, knowledge and attitudes of community pharmacists in Jordan towards diabetes and its management. The validated diabetes knowledge survey tool obtained from Simpson et al, 2009 was modified to suit the Jordanian population of community pharmacists. It contains two sections related to the services that pharmacists provided to diabetics patients and attitude toward health care professionals. The random sampling selection method was used and oral interviews using modified questionnaires were administered to measure the attitudes of pharmacists in Jordan towards diabetes. Random selection was achieved via numbering lists of 1,000 community pharmacists with 500 being chosen randomly across the country. In a total of 422 completed survey （84.4%）, more than 60% of the pharmacists showed that they ＂sometimes＂ counsel diabetic patients. In addition, home blood glucose monitoring was promoted by around half of them. Only a small part of them showed that that they checked prescriptions for drug interactions. The most of them showed not to provide patients with information regarding insulin use and storage. The most of them showed that absence of time and lack of continuous education programs are the main barriers limiting community interaction with diabetic patients. Pharmacists should be provided with continuous diabetes education programs to increase and enhance their counseling skills. The community pharmacists should play a greater role toward the well being of diabetic patients.展开更多
Background:Diabetes and hypertension have been identified as risk factors for HCV complications in previous studies.This has sparked the interest in the field of prevention by identifying at-risk individuals and incre...Background:Diabetes and hypertension have been identified as risk factors for HCV complications in previous studies.This has sparked the interest in the field of prevention by identifying at-risk individuals and increasing investments for screening among pharmacists.The aim of this study was to screen for risk factors,including age,gender,BMI,hypertension,diabetes,and obesity,in Egyptian patients with HCV Methods:A prospective cross-sectional study was carried out from September 2018 to February 2019,with a total of 1,959 medical records collected.By comparing the patients'characteristics,variables related to metabolic risk,and body composition measurements,regression models have been established to determine any confounding factors.Results:The prevalence of HCV antibody was 41.0%in men and 59.0%in women.Among the variables included in the regression analysis,age,BMI,and uncontrolled hypertension were found to have statistically significant associations with diabetes in HCV positive cases(p<0.001).HCV patients>40 years old with high BMI were found to have significant associations with both,diabetes and hypertension(p<0.001).Hypertensive HCV patients were found to have significant associations with gender,age>40,and DM(p<0.001).Conclusion:HCV infection and metabolic disorders have a closed cycle relationship.Reducing the complications of DM has a promising prospective of limiting the complications of HCV .展开更多
Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen so...Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen source for nourishment.They are mainly transported by oligopeptide transporter-1(PepT-1)which are primarily expressed in the intestine with the characteristics of high-capacity and low energy consumption.Our preliminary research discovered the transmembrane transport of SLN could be improved by stimulating the oligopeptide absorption pathway.This implied the potential of combining the advantages of SLN with oligopeptide transporter mediated transportation.Herein,two kinds of dipeptide modified SLN were designed with insulin and glucagon like peptide-1(GLP-1)analogue exenatide as model drugs.These drugs loaded SLN showed enhanced oral bioavailability and hypoglycemic effect in both type I diabetic C57BL/6mice and type II diabetic KKAymice.Compared with un-modified SLN,dipeptide-modified SLN could be internalized by intestinal epithelial cells via PepT-1-mediated endocytosis with higher uptake.Interestingly,after internalization,more SLN could access the systemic circulation via lymphatic transport pathway,highlighting the potential to combine the oligopeptide-absorption route with SLN for oral drug delivery.展开更多
Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-cateni...Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-catenin(WβC)signaling pathway,a crucial player in neurogenesis,neuronal survival,and synaptic plasticity,is involved in several cellular mechanisms related to NDs.Dysregulation of this pathway is a hallmark in the development of various NDs.This study explores multiple polyphenolic compounds,such as flavonoids,stilbenes,lignans,and phenolic acids,and their potential to protect the nervous system.It provides a comprehensive analysis of their effects on the WβC pathway,elucidating their modes of action.The study highlights the dual function of polyphenols in regulating and protecting the nervous system,providing reassurance about the research benefits.This review provides a comprehensive analysis of the results obtained from both in vitro studies and in vivo research,shedding light on how these substances influence the various components of the pathway.The focus is mainly on the molecular mechanisms that allow polyphenols to reduce oxidative stress,inflammation,and apoptotic processes,ultimately improving the function and survival of neurons.This study aims to offer a thorough understanding of the potential of polyphenols in targeting the WβC signaling pathway,which could lead to the development of innovative therapeutic options for NDs.展开更多
Depression is a common psychiatric condition with a considerable influence on global health.Although current pharmacotherapeutic choices are of indisputable relevance,there is sustained interest in natural medicines f...Depression is a common psychiatric condition with a considerable influence on global health.Although current pharmacotherapeutic choices are of indisputable relevance,there is sustained interest in natural medicines for treating depressive symptoms.Polyphenols,a class of plant-derived natural compounds,have received attention due to their possible neuroprotective and anti-depressive properties.In this review,we aimed to present the intricate mechanisms through which polyphenols modulate inflammation,neurogenesis,oxidative stress,and the gut microbiota.Consumption of polyphenol-rich diets is emerging as a non-invasive,natural,and cost-effective approach to supporting brain health,with potential influence on depressive symptoms.While there have been promising results,more research is needed to draw solid conclusions regarding the medicinal potential of polyphenols.展开更多
Background:Chaetomorpha aerea,a marine green alga,has drawn attention because of its rich phytochemical constituents and therapeutic benefits.Using an integrated approach that combined in vitro,in vivo,and in silico a...Background:Chaetomorpha aerea,a marine green alga,has drawn attention because of its rich phytochemical constituents and therapeutic benefits.Using an integrated approach that combined in vitro,in vivo,and in silico approaches,this work examined the antioxidant,anti-inflammatory,and antidiabetic qualities of acetone extract of C.aerea(AECA).Methods:Total phenolic and flavonoid concentrations of AECA were measured.Antioxidant activity was assessed using the DPPH and ABTS free radical scavenging assays.In vitro protein denaturation and in vivo carrageenan-induced paw edema models were employed to evaluate the anti-inflammatory potential,whereas antidiabetic activity was assessed using in vitroα-amylase inhibition and in vivo oral glucose tolerance test(OGTT).Molecular docking and ADME/T analysis were employed to further analyze bioactive compounds identified using gas chromatography–mass spectrometry(GC–MS).Result:Antioxidant activity demonstrated a minimum inhibitory concentration(IC_(50))of 107.44μg/mL for DPPH and 118.23μg/mL for ABTS.In vitro anti-inflammatory assays indicated a suppression of protein denaturation at a concentration of 102μg/mL(IC_(50)),where AECA(400 mg/kg)resulted in a 27%reduction in paw edema at 6 h in the mouse model.In vitro antidiabetic test indicatedα-amylase inhibition with an IC_(50) value of 70.72μg/mL,and in the OGTT,a significant lowering of blood glucose was recorded at 120 min in mice.Strong binding affinities were observed for stigmasta-5,24(28)-dien-3-ol,identified using GC–MS,with values of−9.9 kcal/mol forα-amylase and−8.0 kcal/mol for cyclooxygenase-2.Conclusion:C.aerea serves as an effective natural remedy for oxidative stress,inflammation,and hyperglycemia.These findings advocate for further clinical and mechanistic investigations to optimize therapeutic efficacy.展开更多
Objective:To evaluate the antidiabetic effect of Salsola imbricata(S.imbricata)leaf extract against high-fat-diet/streptozocin-induced alterations in diabetic rats and to explore the underlying mechanisms involved in ...Objective:To evaluate the antidiabetic effect of Salsola imbricata(S.imbricata)leaf extract against high-fat-diet/streptozocin-induced alterations in diabetic rats and to explore the underlying mechanisms involved in insulin secretion.Methods:The total phytochemical content of ethyl acetate extract of S.imbricata was analyzed by HPLC.In vitro antioxidant and antidiabetic activities were determined.Ethyl acetate extract of S.imbricata(250 and 500 mg/kg)was administered to diabetic rats for 21 days.Serum glucose,serum insulin,fasting blood glucose,body weight,and homeostasis model assessment of insulin resistance were measured.The hepatic malondialdehyde and antioxidant enzyme activities including superoxide dismutase,catalase,and glutathione peroxidase were evaluated.Sandwich ELISA kits were used to measure pro-inflammatory cytokines IL-6 and tumor necrosis factor-α(TNF-α)in liver tissue homogenate.Pdx-1,Ins-1,and Ins-2 expression levels were assessed using qRT-PCR.Results:S.imbricata had potent antioxidant(IC50=11.75µg/mL)and antidiabetic activity(IC50=28.10µg/mL).HPLC analysis showed the presence of gallic acid,p-coumaric acid,salicylic acid,chlorogenic acid,caffeic acid,and quercetin.S.imbricata extract significantly(P<0.05)reduced blood glucose levels with marked improvement in insulin sensitivity and reduced insulin resistance.S.imbricata leaf extract improved malondialdehyde,superoxide dismutase,catalase,and glutathione peroxidase levels in hepatic tissue.S.imbricata leaf extract also decreased levels of TNF-αand IL-6(P<0.05).qRT-PCR revealed the upregulation of insulin signaling transduction genes(Pdx-1,Ins-1,Ins-2).Conclusions:S.imbricata ethyl acetate extract exhibits pronounced antidiabetic activity in rats by improving insulin resistance via modulation of insulin signaling pathway and alleviating oxidative stress.展开更多
Natural products(NPs)have long been recognized for their therapeutic potential,especially in cancer treatment,due to an ability to interact with multiple cellular pathways.The identification of molecular targets for N...Natural products(NPs)have long been recognized for their therapeutic potential,especially in cancer treatment,due to an ability to interact with multiple cellular pathways.The identification of molecular targets for NPs is a critical step in understanding anticancer mechanisms,with chemical proteomics emerging as a powerful approach.Both label-based and-free proteomic techniques have been utilized to identify these targets,each with their own advantages and limitations.While label-based methods provide high specificity through chemical tagging,the requirement for labeling can be a limitation,potentially altering NP natural properties.Conversely,label-free techniques allow for the detection of NP-protein interactions without structural modification but may struggle with transient interactions or low-abundance targets.Recent advances in artificial intelligence(AI)have further enhanced the field by improving target prediction and streamlining data analysis.AI-driven models,especially machine learning algorithms,have proven effective in processing complex proteomic data and predicting potential NP-protein interactions.The integration of AI with chemical proteomics accelerates target identification and deepens our understanding of the molecular mechanisms underlying the anticancer effects of NPs.This review explores the application of chemical proteomics and AI in the identification of cancer-related targets for NPs,highlighting current challenges and future directions for clinical translation.展开更多
Introduction: In recent times, satisfaction studies have gained importance in the health sector as a way to monitor services and products. The main aim of this study was to explore patient satisfaction with pharmaceut...Introduction: In recent times, satisfaction studies have gained importance in the health sector as a way to monitor services and products. The main aim of this study was to explore patient satisfaction with pharmaceutical care provided in Nampula healthcare centers. Material and Methods: The study was conducted at the 25 de Setembro, 1˚ de Maio, and Muhala-Expansão healthcare centers in Nampula. The sample consisted of 381 patients, with 127 from each center, selected for accessibility. Data were collected through a questionnaire with an internal consistency of 0.816, calculated using McDonald’s total Omega (ωt). The analysis included frequencies, descriptive statistics (mean and standard deviation), and inferential statistics like Binary Logistic Regression. Results: Overall satisfaction was 3.62 ± 0.627 on a scale of 1 to 5, or 69.8%. The binary regression associated a higher education level with dissatisfaction (COR 0.204, 95% CI: −2.752 to −0.427) and living in Marrere (COR 0.083, 95% CI: -5.098 to 0.120) and Muahivir-Expansão (COR 0.589, 95% CI: −1.824 to 0.767) with dissatisfaction as well. Conclusion: Satisfaction was generally high, mainly influenced by the availability of medicines and medical supplies, and less by other factors such as healthcare center accessibility, facility quality, and relationships with pharmacy professionals. Although variables like sex, religion, age, marital status, profession, occupation, and the number of pharmacy visits in the last five years were not statistically significant for general satisfaction in this study, they should be considered in future studies as they are often linked to pharmaceutical satisfaction.展开更多
Objective:This study aims to determine the effectiveness of giving a combination of Fe tablets and beetroot juice in increasing hemoglobin(Hb)levels of pregnant women with anemia in the Mataram City area.Methods:This ...Objective:This study aims to determine the effectiveness of giving a combination of Fe tablets and beetroot juice in increasing hemoglobin(Hb)levels of pregnant women with anemia in the Mataram City area.Methods:This study was designed with quasi-experimental design with pre-test and post-test with control design.The location of this study was conducted in the city of Mataram on pregnant women with anemia.The sample of this study was pregnant women with mild anemia based on inclusion and exclusion criteria,divided into 2 groups:a control group and a treatment group of 15 respondents each,bringing the total respondents to 30 people.Analysis of Hb level measurement results was carried out using the independent sample t-test.Results:The results obtained in the treatment group(combination of beet juice and Fe tablets)were the mean pre-test of 9.93 mg/dL and post-test of 11.90 mg/dL(P-value=0.000),which means there is effectiveness in increasing hemoglobin levels while in the control group.Comparison of increased Hb levels of the control group and significantly different treatments marked by a P value of 0.001.Conclusions:the combination of Fe tablets and beetroot juice is effective in increasing Hb levels of pregnant women with anemia in the Mataram City area.展开更多
High-altitude pulmonary hypertension(HAPH)occurs when blood pressure in the pulmonary arteries rises due to exposure to high altitudes above 2,500 m.At these elevations,reduced atmospheric pressure leads to lower oxyg...High-altitude pulmonary hypertension(HAPH)occurs when blood pressure in the pulmonary arteries rises due to exposure to high altitudes above 2,500 m.At these elevations,reduced atmospheric pressure leads to lower oxygen levels,triggering a series of physiological responses,including pulmonary artery constriction,which elevates blood pressure.This review explored the complex pathophysiological mechanisms of HAPH and reviewed current pharmaceutical interventions for its management.Meanwhile,this review particularly emphasized on the emerging research concerning Chinese medicinal plants as potential treatments for HAPH.Traditional Chinese medicines are rich in diverse natural ingredients that show significant promise in alleviating HAPH symptoms.We reviewed both in vitro and in vivo studies to assess the efficacy,safety,and mechanisms of these natural medicines,along with their potential adverse effects.Additionally,this review highlighted new alternative natural remedies,underscoring the need for ongoing research to expand available treatment options for HAPH.展开更多
Objective:To evaluate and compare the quality of life(QoL)in patients with multidrug-resistant(MDR-TB)and drug-sensitive(DS-TB)as well as to investigate factors associated with QoL among MDR-TB patients in real-world ...Objective:To evaluate and compare the quality of life(QoL)in patients with multidrug-resistant(MDR-TB)and drug-sensitive(DS-TB)as well as to investigate factors associated with QoL among MDR-TB patients in real-world scenarios at the Haji Hospital,Surabaya.Methods:We conducted a case-control study from June to December 2024.MDR-TB and DS-TB patients were classified into case and control groups,respectively.We used the World Health Organization’s Quality of Life Brief(WHOQOL-BREF)instrument and Patient Health Questionnaire-9(PHQ-9)to assess QoL and depression levels,respectively.Multivariate analysis was used to analyze factors associated with QoL of patients with MDR-TB.Results:Forty-one patients with MDR-TB and 43 with DS-TB were enrolled in the study.A mean score for all domains(physical,psychological,social relationship,environmental)and total mean score of WHOQOL-BREF was significantly lower in MDR-TB than those with DS-TB(P<0.05).The prevalence of depression and the mean score of PHQ-9 were significantly higher in MDR-TB than in DS-TB(P<0.05).PHQ-9 negatively correlates with the WHOQOL-BREF score(r=-0.502,P<0.05)among MDR-TB patients.MDR-TB patients with depression were significantly associated with low QoL in the physical(OR 3.611;95%CI 2.393-6.951;P=0.029),psychological(OR 1.672;95%CI 1.179-5.941;P=0.021),social relationship(OR 2.586;95%CI 1.611-2.909;P=0.014),and environmental domains(OR 1.926;95%CI 1.047-2.147;P=0.048).Conclusions:MDR-TB patients had worse QoL than DS-TB.Those with depression were associated with low QoL.Strategies that identify and tackle alterations in the QoL for MDR-TB patients are necessary during TB treatment.展开更多
Osteoarthritis(OA)is a chronic joint disease characterized by cartilage degradation,synovial inflammation,and subchondral bone remodelling.Despite its increasing prevalence,effective diagnostic,disease-limiting,and th...Osteoarthritis(OA)is a chronic joint disease characterized by cartilage degradation,synovial inflammation,and subchondral bone remodelling.Despite its increasing prevalence,effective diagnostic,disease-limiting,and therapeutic strategies remain unattainable.Recent studies have recognized the involvement of microRNA-155(miR-155)in the pathogenesis of OA and most of its risk factors while also identifying the antidiabetic drug metformin as a potential modulator of disease progression.MiR-155,a key endogenous regulator of the immune system,mechano-transduction,and multiple genetic pathways,interacts with OA targets of cellular energetic and circadian homeostasis,promoting systemic and local articular inflammation,cartilage matrix degradation,and chondrocyte apoptosis.Metformin,widely used for type 2 diabetes,has demonstrated anti-inflammatory,anti-oxidative,and chondroprotective properties in OA,mainly through its activation of adenosine monophosphate-activated protein kinase and inhibition of nuclear factor kappa-B signalling.Enthrallingly,metformin targets the same cellular pathways as miR-155 with emerging evidence also suggesting miR-155 expression modulation,indicating synergistic,potentially disease-modifying effects in OA.This review highlights the central role of miR-155 in OA pathophysiology and its potential as a biomarker for disease diagnosis and progression.MiR-155 targeting-through microRNA therapeutics(mimics/antagomiRs)and/or metformin-could pave the way for innovative treatments,including novel articular delivery systems and cell-based therapies.展开更多
Objective:To estimate the willingness to pay(WTP)of Ho Chi Minh City residents for the hand,foot,and mouth disease(HFMD)vaccine and its associated factors using the contingent valuation method.Methods:This cross-secti...Objective:To estimate the willingness to pay(WTP)of Ho Chi Minh City residents for the hand,foot,and mouth disease(HFMD)vaccine and its associated factors using the contingent valuation method.Methods:This cross-sectional study was conducted in 2024,involved face-to-face interviews with 423 participants in Ho Chi Minh City.The participants were divided into two groups:parents of children under six and individuals without young children.WTP for the HFMD vaccine was assessed using the Krinsky and Robb procedure and the double-bound dichotomous choice technique.A probit regression model was used to analyze factors influencing WTP.Results:The participants had a mean age of(34.0±10.3)years,and the majority of them were female,resided in urban areas,and held a university degree.54.6%had children under six years of age,and 63.8%had never heard of the EV71 vaccine.The mean WTP for two doses of the HFMD vaccine was VND 1240000(USD 51.66).Parents of children under six years old had a mean WTP of USD 49.16,while individuals without young children had a mean WTP of USD 56.25.Significant factors that were positively associated with WTP included vaccine price,younger age,higher income,and greater knowledge about vaccines.Conclusions:The study indicates a relatively high willingness to pay for HFMD vaccination in Ho Chi Minh City,suggesting strong potential for vaccine implementation.It is recommended that the government disseminate vaccine-related information to enhance public awareness and understanding.展开更多
Hematological cancer stem cells(HCSCs)is a subpopulation of cells within hematological cancers that,through their characteristics,enhance malignancy and render their therapy more challenging.By uncovering the underlyi...Hematological cancer stem cells(HCSCs)is a subpopulation of cells within hematological cancers that,through their characteristics,enhance malignancy and render their therapy more challenging.By uncovering the underlying mechanisms behind characteristic properties such as self-renewal,immune evasion,and conventional therapy resistance,as well as the major differences between other cancers and physiological cells,new and alternative targets can be assessed for use in existing and novel immunotherapeutic interventions.Through the evaluation of the existing literature,one can realize that there have already been several studies addressing the use of stem cell transplantation(SCT),monoclonal antibodies(mAbs),cell therapies,cancer vaccines,and oncolytic viruses,with varying degrees of success.As such,this study aims to combine existing information and clinical evidence to assess and bring to the spotlight targets related toHCSCs that can be considered for the improvement of therapeutic interventions.展开更多
Objective:HIV has infected approximately 75 million people worldwide with over half dying from AIDS-related diseases.This study aimed to determine individuals'willingness to pay(WTP)for future HIV vaccines.Methods...Objective:HIV has infected approximately 75 million people worldwide with over half dying from AIDS-related diseases.This study aimed to determine individuals'willingness to pay(WTP)for future HIV vaccines.Methods:A cross sectional study was conducted in December 2022 in Southern Vietnam with 1675 face-to-face interviews.WTP was determined using the contingent valuation method with two bidding games under three vaccine efficacy scenarios(high,medium,low)for both self-vaccination and child vaccination.Results:Among 1655 valid respondents,553 were willing to pay for their children's vaccination.Overall,the WTP of adults for the HIV vaccine was(4961264±3793652)VND(23700 VND=1 US dollar).The WTP of parents is(4947799±4930721)VND for self-vaccination and(4865399±4064567)VND for vaccinating their children.Average WTP decreased with lower vaccine efficacy and lower bid prices.Education level,marital status,occupation,and monthly income were significantly associated with WTP for all vaccination types.Conclusions:In this study,high WTP rates and numerous individuals willing to pay for HIV vaccines were found.These findings can help decision-makers understand factors influencing WTP for future HIV vaccines and provide evidence for developing funding programs and budgeting plans for introducing such vaccines in Vietnam.展开更多
The Clp/Hsp100 family,part of the ATPase associated with various cellular activities(AAA+)superfamily,includes caseinolytic peptidase B(ClpB),a highly conserved protein found in bacteria,fungi,protozoa,and plants.Nota...The Clp/Hsp100 family,part of the ATPase associated with various cellular activities(AAA+)superfamily,includes caseinolytic peptidase B(ClpB),a highly conserved protein found in bacteria,fungi,protozoa,and plants.Notably,ClpB is present in all ESKAPE pathogens:Enterococcus faecium,Staphylococcus aureus,Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa,and Enterobacter spp.ClpB plays a crucial role in reactivating and disaggregating proteins,enabling pathogens to survive under host-induced stress and conferring thermotolerance to bacterial cells.Infections caused by ESKAPE pathogens are particularly challenging due to their resistance to broad-spectrum antibiotics and biofilm formation,posing a significant global health threat as they are often multidrug-resistant,extensively drug-resistant,and pan-drug-resistant.Given its absence in human cells and its essential role in bacterial survival under stress,ClpB is a promising target for antimicrobial therapy.Targeting Hsp100 family proteins could lead to the development of novel antifungal and antiprotozoal treatments.This review explores the function of ClpB in the survival of ESKAPE pathogens and the protozoan Plasmodium falciparum.Relevant research findings were compiled using academic databases,and data analysis was performed using Clustal Omega Multiple Sequence Alignment and Boxshade tools.展开更多
Oral squamous cell carcinoma(OSCC)is the most common manifestation of oral cancer.It has been proposed that periodontal pathogens contribute to OSCC progression,mainly by their virulence factors.However,the main perio...Oral squamous cell carcinoma(OSCC)is the most common manifestation of oral cancer.It has been proposed that periodontal pathogens contribute to OSCC progression,mainly by their virulence factors.However,the main periodontal pathogen and its mechanism to modulate OSCC cells remains not fully understood.In this study we investigate the main host-pathogen pathways in OSCC by computational proteomics and the mechanism behind cancer progression by the oral microbiome.The main hostpathogen pathways were analyzed in the secretome of biopsies from patients with OSCC and healthy controls by mass spectrometry.Then,functional assays were performed to evaluate the host-pathogen pathways highlighted in oral cancer.Host proteins associated with LPS response,cell migration/adhesion,and metabolism of amino acids were significantly upregulated in the human cancer proteome,whereas the complement cascade was downregulated in malignant samples.Then,the microbiome analysis revealed large number and variety of peptides from Fusobacterium nucleatum(F.nucleatum)in OSCC samples,from which several enzymes from the L-glutamate degradation pathway were found,indicating that L-glutamate from cancer cells is used as an energy source,and catabolized into butyrate by the bacteria.In fact,we observed that F.nucleatum modulates the cystine/glutamate antiporter in an OSCC cell line by increasing SLC7A11 expression,promoting L-glutamate efflux and favoring bacterial infection.Finally,our results showed that F.nucleatum and its metabolic derivates promote tumor spheroids growth,spheroidsderived cell detachment,epithelial-mesenchymal transition and Galectin-9 upregulation.Altogether,F.nucleatum promotes protumoral mechanism in oral cancer.展开更多
This study aims to enhance the mechanical properties,disintegration,and dissolution rates of crosslinked carrageenan(CRG)capsule shells by shortening the long chains of CRG through a hydrolysis reaction with citric ac...This study aims to enhance the mechanical properties,disintegration,and dissolution rates of crosslinked carrageenan(CRG)capsule shells by shortening the long chains of CRG through a hydrolysis reaction with citric acid(CA).The hydrolysis of CRG was carried out using varying concentrations of CA,resulting in hydrolyzed CRG(HCRG).This was followed by cross-linking with xanthan gum(XG)and the addition of sorbitol(SOR)as a plasticizer.The results indicated that the optimal swelling capacity of HCRG-XG/SOR hard-shell capsules occurred at a CA concentration of 0.5%,achieving a maximum swelling rate of 445.39%after 15 min.Additionally,the best capsule hardness was alsomeasured at this CA concentration,reaching a hardness level of 480.157 g(F=4.67 N).FTIR analysis demonstrated that the presence of the acid group from CA altered the composition of the CRG chains.Furthermore,SEM-EDX mapping analysis revealed that the surface morphology of the synthesized capsules exhibited a relatively smooth texture with a limited number and size of pores,resulting in good capsule stability for drug delivery.Thein vitro disintegration and dissolution rates of theHCRG-XG/SOR capsuleswere observed to be the fastest and highest atpH1.2,respectively.The disintegration time was recorded at 20 min and 46 s,while the dissolution test indicated a drug release of 78.08%after 5min and 100%after 120 min.The drug delivery kinetics ofHCRG-XG/SOR followed the Ritger-Peppas model,indicating a complex release mechanism that involved swelling,diffusion,erosion,and capsule disintegration.展开更多
基金supported by the National Institute of Health/National Eye Institute(NIH/NEI)grants(R00 EY029373,R01 EY035658)to AYFKnights Templar Eye Foundation Research Grant to ESIntramural UAMS Hornick and Sturgis grants to AYF and ES respectively。
文摘Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Ischemic retinopathy can be acute,such as in central or branch retinal artery occlusion,or chronic,such as with DR(Figure 1).Although the causes of retinopathies are diverse,one pathogenic event shared by these conditions is the myeloid cell response to retinal ischemia(Shahror et al.,2024a).
文摘To measure the experiences, knowledge and attitudes of community pharmacists in Jordan towards diabetes and its management. The validated diabetes knowledge survey tool obtained from Simpson et al, 2009 was modified to suit the Jordanian population of community pharmacists. It contains two sections related to the services that pharmacists provided to diabetics patients and attitude toward health care professionals. The random sampling selection method was used and oral interviews using modified questionnaires were administered to measure the attitudes of pharmacists in Jordan towards diabetes. Random selection was achieved via numbering lists of 1,000 community pharmacists with 500 being chosen randomly across the country. In a total of 422 completed survey （84.4%）, more than 60% of the pharmacists showed that they ＂sometimes＂ counsel diabetic patients. In addition, home blood glucose monitoring was promoted by around half of them. Only a small part of them showed that that they checked prescriptions for drug interactions. The most of them showed not to provide patients with information regarding insulin use and storage. The most of them showed that absence of time and lack of continuous education programs are the main barriers limiting community interaction with diabetic patients. Pharmacists should be provided with continuous diabetes education programs to increase and enhance their counseling skills. The community pharmacists should play a greater role toward the well being of diabetic patients.
文摘Background:Diabetes and hypertension have been identified as risk factors for HCV complications in previous studies.This has sparked the interest in the field of prevention by identifying at-risk individuals and increasing investments for screening among pharmacists.The aim of this study was to screen for risk factors,including age,gender,BMI,hypertension,diabetes,and obesity,in Egyptian patients with HCV Methods:A prospective cross-sectional study was carried out from September 2018 to February 2019,with a total of 1,959 medical records collected.By comparing the patients'characteristics,variables related to metabolic risk,and body composition measurements,regression models have been established to determine any confounding factors.Results:The prevalence of HCV antibody was 41.0%in men and 59.0%in women.Among the variables included in the regression analysis,age,BMI,and uncontrolled hypertension were found to have statistically significant associations with diabetes in HCV positive cases(p<0.001).HCV patients>40 years old with high BMI were found to have significant associations with both,diabetes and hypertension(p<0.001).Hypertensive HCV patients were found to have significant associations with gender,age>40,and DM(p<0.001).Conclusion:HCV infection and metabolic disorders have a closed cycle relationship.Reducing the complications of DM has a promising prospective of limiting the complications of HCV .
基金supported by National Key Research and Development Program of China(Grant No.2021YFE0115200)the Regional Innovation and Development Joint Fund of National Natural Science Foundation of China(Grant No.U22A20356).
文摘Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen source for nourishment.They are mainly transported by oligopeptide transporter-1(PepT-1)which are primarily expressed in the intestine with the characteristics of high-capacity and low energy consumption.Our preliminary research discovered the transmembrane transport of SLN could be improved by stimulating the oligopeptide absorption pathway.This implied the potential of combining the advantages of SLN with oligopeptide transporter mediated transportation.Herein,two kinds of dipeptide modified SLN were designed with insulin and glucagon like peptide-1(GLP-1)analogue exenatide as model drugs.These drugs loaded SLN showed enhanced oral bioavailability and hypoglycemic effect in both type I diabetic C57BL/6mice and type II diabetic KKAymice.Compared with un-modified SLN,dipeptide-modified SLN could be internalized by intestinal epithelial cells via PepT-1-mediated endocytosis with higher uptake.Interestingly,after internalization,more SLN could access the systemic circulation via lymphatic transport pathway,highlighting the potential to combine the oligopeptide-absorption route with SLN for oral drug delivery.
基金financially supporting this work through the Large Research Group Project under Grant no.R.G.P.2/509/45
文摘Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-catenin(WβC)signaling pathway,a crucial player in neurogenesis,neuronal survival,and synaptic plasticity,is involved in several cellular mechanisms related to NDs.Dysregulation of this pathway is a hallmark in the development of various NDs.This study explores multiple polyphenolic compounds,such as flavonoids,stilbenes,lignans,and phenolic acids,and their potential to protect the nervous system.It provides a comprehensive analysis of their effects on the WβC pathway,elucidating their modes of action.The study highlights the dual function of polyphenols in regulating and protecting the nervous system,providing reassurance about the research benefits.This review provides a comprehensive analysis of the results obtained from both in vitro studies and in vivo research,shedding light on how these substances influence the various components of the pathway.The focus is mainly on the molecular mechanisms that allow polyphenols to reduce oxidative stress,inflammation,and apoptotic processes,ultimately improving the function and survival of neurons.This study aims to offer a thorough understanding of the potential of polyphenols in targeting the WβC signaling pathway,which could lead to the development of innovative therapeutic options for NDs.
基金Supported by the Ministry of Science,Technological Development and Innovation of the Republic of Serbia,No.451-03-137/2025-03/200111 and No.451-03-137/2025-03/200146.
文摘Depression is a common psychiatric condition with a considerable influence on global health.Although current pharmacotherapeutic choices are of indisputable relevance,there is sustained interest in natural medicines for treating depressive symptoms.Polyphenols,a class of plant-derived natural compounds,have received attention due to their possible neuroprotective and anti-depressive properties.In this review,we aimed to present the intricate mechanisms through which polyphenols modulate inflammation,neurogenesis,oxidative stress,and the gut microbiota.Consumption of polyphenol-rich diets is emerging as a non-invasive,natural,and cost-effective approach to supporting brain health,with potential influence on depressive symptoms.While there have been promising results,more research is needed to draw solid conclusions regarding the medicinal potential of polyphenols.
文摘Background:Chaetomorpha aerea,a marine green alga,has drawn attention because of its rich phytochemical constituents and therapeutic benefits.Using an integrated approach that combined in vitro,in vivo,and in silico approaches,this work examined the antioxidant,anti-inflammatory,and antidiabetic qualities of acetone extract of C.aerea(AECA).Methods:Total phenolic and flavonoid concentrations of AECA were measured.Antioxidant activity was assessed using the DPPH and ABTS free radical scavenging assays.In vitro protein denaturation and in vivo carrageenan-induced paw edema models were employed to evaluate the anti-inflammatory potential,whereas antidiabetic activity was assessed using in vitroα-amylase inhibition and in vivo oral glucose tolerance test(OGTT).Molecular docking and ADME/T analysis were employed to further analyze bioactive compounds identified using gas chromatography–mass spectrometry(GC–MS).Result:Antioxidant activity demonstrated a minimum inhibitory concentration(IC_(50))of 107.44μg/mL for DPPH and 118.23μg/mL for ABTS.In vitro anti-inflammatory assays indicated a suppression of protein denaturation at a concentration of 102μg/mL(IC_(50)),where AECA(400 mg/kg)resulted in a 27%reduction in paw edema at 6 h in the mouse model.In vitro antidiabetic test indicatedα-amylase inhibition with an IC_(50) value of 70.72μg/mL,and in the OGTT,a significant lowering of blood glucose was recorded at 120 min in mice.Strong binding affinities were observed for stigmasta-5,24(28)-dien-3-ol,identified using GC–MS,with values of−9.9 kcal/mol forα-amylase and−8.0 kcal/mol for cyclooxygenase-2.Conclusion:C.aerea serves as an effective natural remedy for oxidative stress,inflammation,and hyperglycemia.These findings advocate for further clinical and mechanistic investigations to optimize therapeutic efficacy.
文摘Objective:To evaluate the antidiabetic effect of Salsola imbricata(S.imbricata)leaf extract against high-fat-diet/streptozocin-induced alterations in diabetic rats and to explore the underlying mechanisms involved in insulin secretion.Methods:The total phytochemical content of ethyl acetate extract of S.imbricata was analyzed by HPLC.In vitro antioxidant and antidiabetic activities were determined.Ethyl acetate extract of S.imbricata(250 and 500 mg/kg)was administered to diabetic rats for 21 days.Serum glucose,serum insulin,fasting blood glucose,body weight,and homeostasis model assessment of insulin resistance were measured.The hepatic malondialdehyde and antioxidant enzyme activities including superoxide dismutase,catalase,and glutathione peroxidase were evaluated.Sandwich ELISA kits were used to measure pro-inflammatory cytokines IL-6 and tumor necrosis factor-α(TNF-α)in liver tissue homogenate.Pdx-1,Ins-1,and Ins-2 expression levels were assessed using qRT-PCR.Results:S.imbricata had potent antioxidant(IC50=11.75µg/mL)and antidiabetic activity(IC50=28.10µg/mL).HPLC analysis showed the presence of gallic acid,p-coumaric acid,salicylic acid,chlorogenic acid,caffeic acid,and quercetin.S.imbricata extract significantly(P<0.05)reduced blood glucose levels with marked improvement in insulin sensitivity and reduced insulin resistance.S.imbricata leaf extract improved malondialdehyde,superoxide dismutase,catalase,and glutathione peroxidase levels in hepatic tissue.S.imbricata leaf extract also decreased levels of TNF-αand IL-6(P<0.05).qRT-PCR revealed the upregulation of insulin signaling transduction genes(Pdx-1,Ins-1,Ins-2).Conclusions:S.imbricata ethyl acetate extract exhibits pronounced antidiabetic activity in rats by improving insulin resistance via modulation of insulin signaling pathway and alleviating oxidative stress.
基金supported in part by the Science and Technology Development Fund,Macao SAR(0098/2021/A2 and 0048/2023/AFJ)the Chinese Medicine Guangdong Laboratory(HQCML-C-2024006).
文摘Natural products(NPs)have long been recognized for their therapeutic potential,especially in cancer treatment,due to an ability to interact with multiple cellular pathways.The identification of molecular targets for NPs is a critical step in understanding anticancer mechanisms,with chemical proteomics emerging as a powerful approach.Both label-based and-free proteomic techniques have been utilized to identify these targets,each with their own advantages and limitations.While label-based methods provide high specificity through chemical tagging,the requirement for labeling can be a limitation,potentially altering NP natural properties.Conversely,label-free techniques allow for the detection of NP-protein interactions without structural modification but may struggle with transient interactions or low-abundance targets.Recent advances in artificial intelligence(AI)have further enhanced the field by improving target prediction and streamlining data analysis.AI-driven models,especially machine learning algorithms,have proven effective in processing complex proteomic data and predicting potential NP-protein interactions.The integration of AI with chemical proteomics accelerates target identification and deepens our understanding of the molecular mechanisms underlying the anticancer effects of NPs.This review explores the application of chemical proteomics and AI in the identification of cancer-related targets for NPs,highlighting current challenges and future directions for clinical translation.
文摘Introduction: In recent times, satisfaction studies have gained importance in the health sector as a way to monitor services and products. The main aim of this study was to explore patient satisfaction with pharmaceutical care provided in Nampula healthcare centers. Material and Methods: The study was conducted at the 25 de Setembro, 1˚ de Maio, and Muhala-Expansão healthcare centers in Nampula. The sample consisted of 381 patients, with 127 from each center, selected for accessibility. Data were collected through a questionnaire with an internal consistency of 0.816, calculated using McDonald’s total Omega (ωt). The analysis included frequencies, descriptive statistics (mean and standard deviation), and inferential statistics like Binary Logistic Regression. Results: Overall satisfaction was 3.62 ± 0.627 on a scale of 1 to 5, or 69.8%. The binary regression associated a higher education level with dissatisfaction (COR 0.204, 95% CI: −2.752 to −0.427) and living in Marrere (COR 0.083, 95% CI: -5.098 to 0.120) and Muahivir-Expansão (COR 0.589, 95% CI: −1.824 to 0.767) with dissatisfaction as well. Conclusion: Satisfaction was generally high, mainly influenced by the availability of medicines and medical supplies, and less by other factors such as healthcare center accessibility, facility quality, and relationships with pharmacy professionals. Although variables like sex, religion, age, marital status, profession, occupation, and the number of pharmacy visits in the last five years were not statistically significant for general satisfaction in this study, they should be considered in future studies as they are often linked to pharmaceutical satisfaction.
基金supported by Muhammadiyah Research Grant (RisetMu) Batch Ⅵ (No. 1687.186/PD/I.3/D/2022)
文摘Objective:This study aims to determine the effectiveness of giving a combination of Fe tablets and beetroot juice in increasing hemoglobin(Hb)levels of pregnant women with anemia in the Mataram City area.Methods:This study was designed with quasi-experimental design with pre-test and post-test with control design.The location of this study was conducted in the city of Mataram on pregnant women with anemia.The sample of this study was pregnant women with mild anemia based on inclusion and exclusion criteria,divided into 2 groups:a control group and a treatment group of 15 respondents each,bringing the total respondents to 30 people.Analysis of Hb level measurement results was carried out using the independent sample t-test.Results:The results obtained in the treatment group(combination of beet juice and Fe tablets)were the mean pre-test of 9.93 mg/dL and post-test of 11.90 mg/dL(P-value=0.000),which means there is effectiveness in increasing hemoglobin levels while in the control group.Comparison of increased Hb levels of the control group and significantly different treatments marked by a P value of 0.001.Conclusions:the combination of Fe tablets and beetroot juice is effective in increasing Hb levels of pregnant women with anemia in the Mataram City area.
基金supported by the National Natural Science Foundation of China(Grant Nos.:32270690 and 32070671).
文摘High-altitude pulmonary hypertension(HAPH)occurs when blood pressure in the pulmonary arteries rises due to exposure to high altitudes above 2,500 m.At these elevations,reduced atmospheric pressure leads to lower oxygen levels,triggering a series of physiological responses,including pulmonary artery constriction,which elevates blood pressure.This review explored the complex pathophysiological mechanisms of HAPH and reviewed current pharmaceutical interventions for its management.Meanwhile,this review particularly emphasized on the emerging research concerning Chinese medicinal plants as potential treatments for HAPH.Traditional Chinese medicines are rich in diverse natural ingredients that show significant promise in alleviating HAPH symptoms.We reviewed both in vitro and in vivo studies to assess the efficacy,safety,and mechanisms of these natural medicines,along with their potential adverse effects.Additionally,this review highlighted new alternative natural remedies,underscoring the need for ongoing research to expand available treatment options for HAPH.
文摘Objective:To evaluate and compare the quality of life(QoL)in patients with multidrug-resistant(MDR-TB)and drug-sensitive(DS-TB)as well as to investigate factors associated with QoL among MDR-TB patients in real-world scenarios at the Haji Hospital,Surabaya.Methods:We conducted a case-control study from June to December 2024.MDR-TB and DS-TB patients were classified into case and control groups,respectively.We used the World Health Organization’s Quality of Life Brief(WHOQOL-BREF)instrument and Patient Health Questionnaire-9(PHQ-9)to assess QoL and depression levels,respectively.Multivariate analysis was used to analyze factors associated with QoL of patients with MDR-TB.Results:Forty-one patients with MDR-TB and 43 with DS-TB were enrolled in the study.A mean score for all domains(physical,psychological,social relationship,environmental)and total mean score of WHOQOL-BREF was significantly lower in MDR-TB than those with DS-TB(P<0.05).The prevalence of depression and the mean score of PHQ-9 were significantly higher in MDR-TB than in DS-TB(P<0.05).PHQ-9 negatively correlates with the WHOQOL-BREF score(r=-0.502,P<0.05)among MDR-TB patients.MDR-TB patients with depression were significantly associated with low QoL in the physical(OR 3.611;95%CI 2.393-6.951;P=0.029),psychological(OR 1.672;95%CI 1.179-5.941;P=0.021),social relationship(OR 2.586;95%CI 1.611-2.909;P=0.014),and environmental domains(OR 1.926;95%CI 1.047-2.147;P=0.048).Conclusions:MDR-TB patients had worse QoL than DS-TB.Those with depression were associated with low QoL.Strategies that identify and tackle alterations in the QoL for MDR-TB patients are necessary during TB treatment.
文摘Osteoarthritis(OA)is a chronic joint disease characterized by cartilage degradation,synovial inflammation,and subchondral bone remodelling.Despite its increasing prevalence,effective diagnostic,disease-limiting,and therapeutic strategies remain unattainable.Recent studies have recognized the involvement of microRNA-155(miR-155)in the pathogenesis of OA and most of its risk factors while also identifying the antidiabetic drug metformin as a potential modulator of disease progression.MiR-155,a key endogenous regulator of the immune system,mechano-transduction,and multiple genetic pathways,interacts with OA targets of cellular energetic and circadian homeostasis,promoting systemic and local articular inflammation,cartilage matrix degradation,and chondrocyte apoptosis.Metformin,widely used for type 2 diabetes,has demonstrated anti-inflammatory,anti-oxidative,and chondroprotective properties in OA,mainly through its activation of adenosine monophosphate-activated protein kinase and inhibition of nuclear factor kappa-B signalling.Enthrallingly,metformin targets the same cellular pathways as miR-155 with emerging evidence also suggesting miR-155 expression modulation,indicating synergistic,potentially disease-modifying effects in OA.This review highlights the central role of miR-155 in OA pathophysiology and its potential as a biomarker for disease diagnosis and progression.MiR-155 targeting-through microRNA therapeutics(mimics/antagomiRs)and/or metformin-could pave the way for innovative treatments,including novel articular delivery systems and cell-based therapies.
文摘Objective:To estimate the willingness to pay(WTP)of Ho Chi Minh City residents for the hand,foot,and mouth disease(HFMD)vaccine and its associated factors using the contingent valuation method.Methods:This cross-sectional study was conducted in 2024,involved face-to-face interviews with 423 participants in Ho Chi Minh City.The participants were divided into two groups:parents of children under six and individuals without young children.WTP for the HFMD vaccine was assessed using the Krinsky and Robb procedure and the double-bound dichotomous choice technique.A probit regression model was used to analyze factors influencing WTP.Results:The participants had a mean age of(34.0±10.3)years,and the majority of them were female,resided in urban areas,and held a university degree.54.6%had children under six years of age,and 63.8%had never heard of the EV71 vaccine.The mean WTP for two doses of the HFMD vaccine was VND 1240000(USD 51.66).Parents of children under six years old had a mean WTP of USD 49.16,while individuals without young children had a mean WTP of USD 56.25.Significant factors that were positively associated with WTP included vaccine price,younger age,higher income,and greater knowledge about vaccines.Conclusions:The study indicates a relatively high willingness to pay for HFMD vaccination in Ho Chi Minh City,suggesting strong potential for vaccine implementation.It is recommended that the government disseminate vaccine-related information to enhance public awareness and understanding.
文摘Hematological cancer stem cells(HCSCs)is a subpopulation of cells within hematological cancers that,through their characteristics,enhance malignancy and render their therapy more challenging.By uncovering the underlying mechanisms behind characteristic properties such as self-renewal,immune evasion,and conventional therapy resistance,as well as the major differences between other cancers and physiological cells,new and alternative targets can be assessed for use in existing and novel immunotherapeutic interventions.Through the evaluation of the existing literature,one can realize that there have already been several studies addressing the use of stem cell transplantation(SCT),monoclonal antibodies(mAbs),cell therapies,cancer vaccines,and oncolytic viruses,with varying degrees of success.As such,this study aims to combine existing information and clinical evidence to assess and bring to the spotlight targets related toHCSCs that can be considered for the improvement of therapeutic interventions.
文摘Objective:HIV has infected approximately 75 million people worldwide with over half dying from AIDS-related diseases.This study aimed to determine individuals'willingness to pay(WTP)for future HIV vaccines.Methods:A cross sectional study was conducted in December 2022 in Southern Vietnam with 1675 face-to-face interviews.WTP was determined using the contingent valuation method with two bidding games under three vaccine efficacy scenarios(high,medium,low)for both self-vaccination and child vaccination.Results:Among 1655 valid respondents,553 were willing to pay for their children's vaccination.Overall,the WTP of adults for the HIV vaccine was(4961264±3793652)VND(23700 VND=1 US dollar).The WTP of parents is(4947799±4930721)VND for self-vaccination and(4865399±4064567)VND for vaccinating their children.Average WTP decreased with lower vaccine efficacy and lower bid prices.Education level,marital status,occupation,and monthly income were significantly associated with WTP for all vaccination types.Conclusions:In this study,high WTP rates and numerous individuals willing to pay for HIV vaccines were found.These findings can help decision-makers understand factors influencing WTP for future HIV vaccines and provide evidence for developing funding programs and budgeting plans for introducing such vaccines in Vietnam.
文摘The Clp/Hsp100 family,part of the ATPase associated with various cellular activities(AAA+)superfamily,includes caseinolytic peptidase B(ClpB),a highly conserved protein found in bacteria,fungi,protozoa,and plants.Notably,ClpB is present in all ESKAPE pathogens:Enterococcus faecium,Staphylococcus aureus,Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa,and Enterobacter spp.ClpB plays a crucial role in reactivating and disaggregating proteins,enabling pathogens to survive under host-induced stress and conferring thermotolerance to bacterial cells.Infections caused by ESKAPE pathogens are particularly challenging due to their resistance to broad-spectrum antibiotics and biofilm formation,posing a significant global health threat as they are often multidrug-resistant,extensively drug-resistant,and pan-drug-resistant.Given its absence in human cells and its essential role in bacterial survival under stress,ClpB is a promising target for antimicrobial therapy.Targeting Hsp100 family proteins could lead to the development of novel antifungal and antiprotozoal treatments.This review explores the function of ClpB in the survival of ESKAPE pathogens and the protozoan Plasmodium falciparum.Relevant research findings were compiled using academic databases,and data analysis was performed using Clustal Omega Multiple Sequence Alignment and Boxshade tools.
基金supported by Agencia Nacional de Investigación y Desarrollo(ANID),Chilean Government Fondecyt Regular 1211480supported by a Master ANID Scholarship+1 种基金funded by ANID/Fondecyt Regular 1211480funded by EQM150061(FONDEQUIP-ANID)。
文摘Oral squamous cell carcinoma(OSCC)is the most common manifestation of oral cancer.It has been proposed that periodontal pathogens contribute to OSCC progression,mainly by their virulence factors.However,the main periodontal pathogen and its mechanism to modulate OSCC cells remains not fully understood.In this study we investigate the main host-pathogen pathways in OSCC by computational proteomics and the mechanism behind cancer progression by the oral microbiome.The main hostpathogen pathways were analyzed in the secretome of biopsies from patients with OSCC and healthy controls by mass spectrometry.Then,functional assays were performed to evaluate the host-pathogen pathways highlighted in oral cancer.Host proteins associated with LPS response,cell migration/adhesion,and metabolism of amino acids were significantly upregulated in the human cancer proteome,whereas the complement cascade was downregulated in malignant samples.Then,the microbiome analysis revealed large number and variety of peptides from Fusobacterium nucleatum(F.nucleatum)in OSCC samples,from which several enzymes from the L-glutamate degradation pathway were found,indicating that L-glutamate from cancer cells is used as an energy source,and catabolized into butyrate by the bacteria.In fact,we observed that F.nucleatum modulates the cystine/glutamate antiporter in an OSCC cell line by increasing SLC7A11 expression,promoting L-glutamate efflux and favoring bacterial infection.Finally,our results showed that F.nucleatum and its metabolic derivates promote tumor spheroids growth,spheroidsderived cell detachment,epithelial-mesenchymal transition and Galectin-9 upregulation.Altogether,F.nucleatum promotes protumoral mechanism in oral cancer.
基金funded through the Penelitian Unggulan Halal,Airlangga University FY 2024 grant number:987/UN3/2024.
文摘This study aims to enhance the mechanical properties,disintegration,and dissolution rates of crosslinked carrageenan(CRG)capsule shells by shortening the long chains of CRG through a hydrolysis reaction with citric acid(CA).The hydrolysis of CRG was carried out using varying concentrations of CA,resulting in hydrolyzed CRG(HCRG).This was followed by cross-linking with xanthan gum(XG)and the addition of sorbitol(SOR)as a plasticizer.The results indicated that the optimal swelling capacity of HCRG-XG/SOR hard-shell capsules occurred at a CA concentration of 0.5%,achieving a maximum swelling rate of 445.39%after 15 min.Additionally,the best capsule hardness was alsomeasured at this CA concentration,reaching a hardness level of 480.157 g(F=4.67 N).FTIR analysis demonstrated that the presence of the acid group from CA altered the composition of the CRG chains.Furthermore,SEM-EDX mapping analysis revealed that the surface morphology of the synthesized capsules exhibited a relatively smooth texture with a limited number and size of pores,resulting in good capsule stability for drug delivery.Thein vitro disintegration and dissolution rates of theHCRG-XG/SOR capsuleswere observed to be the fastest and highest atpH1.2,respectively.The disintegration time was recorded at 20 min and 46 s,while the dissolution test indicated a drug release of 78.08%after 5min and 100%after 120 min.The drug delivery kinetics ofHCRG-XG/SOR followed the Ritger-Peppas model,indicating a complex release mechanism that involved swelling,diffusion,erosion,and capsule disintegration.
