Context-dependent role of sirtuin 2 in inflammation

Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.

Anti-tumor efficacy of Calculus bovis: Suppressing liver cancer by targeting tumor-associated macrophages

Despite significant advances in our understanding of the molecular pathogenesis of liver cancer and the availability of novel pharmacotherapies,liver cancer remains the fourth leading cause of cancer-related mortality worldwide.Tumor relapse,resistance to current anti-cancer drugs,metastasis,and organ toxicity are the major challenges that prevent considerable improvements in patient survival and quality of life.Calculus bovis(CB),an ancient Chinese medicinal drug,has been used to treat various pathologies,including stroke,convulsion,epilepsy,pain,and cancer.In this editorial,we discuss the research findings recently published by Huang et al on the therapeutic effects of CB in inhibiting the development of liver cancer.Utilizing the comprehensive transcriptomic analyses,in vitro experiments,and in vivo studies,the authors demonstrated that CB treatment inhibits the tumor-promoting M2 phenotype of tumor-associated macrophages via downregulating Wnt pathway.While multiple studies have been performed to explore the molecular mechanisms regulated by CB,this study uniquely shows its role in modulating the M2 phenotype of macrophages present within the tumor microenvironment.This study opens new avenues of future investigations aimed at investigating this drug’s efficacy in various mouse models including the effects of combination therapy,and against drug-resistant tumors.

Piperlongumine in combination with EGFR tyrosine kinase inhibitors for the treatment of lung cancer cells

Objectives:EGFR tyrosine kinase inhibitor(EGFR-TKI)therapies such as erlotinib and gefitinib are approved for the treatment of non-small cell lung cancer(NSCLC).However,the high incidence of acquired resistance to these EGFR-TKIs may preclude their effectiveness.Piperlongumine(PPL),an extract from the long pepper fruit(Piper longum),has been shown to possess anticancer properties.The purpose of the study was to investigate piperlongumine as an anticancer agent and to study a combination treatment approach with EGFR-TKIs against lung cancer cells.Methods:Anticancer efficacy of PPL,erlotinib(ERL),gefitinib(GEF),and cisplatin(CIS)were investigated in H1299 and H1975 cell lines.Cells were treated with PPL,ERL,GEF,and CIS alone,and in combination,cell viability was determined after 72 h.The mechanism of PPL-induced cytotoxicity was investigated via reactive oxygen species(ROS)induction,and apoptosis induction using acridine orange/ethidium bromide staining and flow cytometry.The effect of treatment on EGFR-mediated oncogenic signaling was investigated by immunoblotting for mitogenic and apoptotic markers.Results:PPL exhibited a potent cytotoxic effect in H1299 and H1975 cells compared to ERL,GEF,and CIS.Combination treatments of PPL with GEF and ERL showed significant reductions in cancer cells compared to control in both cell lines,which were associated with apoptotic induction,but without significant ROS induction.Compared to control,PPL with GEF significantly increased apoptotic cell death in H1975as confirmed with flow cytometry.Treatment with PPL alone and in combination induced anti-mitogenic and apoptotic responses at the molecular level.Conclusion:PPL sensitized lung cancer cells to EGFR-TKI and induced potent cytotoxic effects at low concentrations.

Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke:a special outlook on mitochondrial delivery

Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.

The Anticancer Potential of Quassinoids-A Mini-Review

The anticancer potential of quassinoids has attracted a great deal of attention for decades,and scientific data revealing their possible applications in cancer management are continuously increasing in the literature.Aside from the potent cytotoxic and antitumor properties of these degraded triterpenes,several quassinoids have exhibited synergistic effects with anticancer drugs.This article provides an overview of the potential anticancer properties of quassinoids,including their cytotoxic and antitumor activities,mechanisms of action,safety evaluation,and potential benefits in combination with anticancer drugs.

Recognition and quality mapping of traditional herbal drugs:way forward towards artificial intelligence

The use of traditional herbal drugs derived from natural sources is on the rise due to their minimal side effects and numerous health benefits.However,a major limitation is the lack of standardized knowledge for identifying and mapping the quality of these herbal medicines.This article aims to provide practical insights into the application of artificial intelligence for quality-based commercialization of raw herbal drugs.It focuses on feature extraction methods,image processing techniques,and the preparation of herbal images for compatibility with machine learning models.The article discusses commonly used image processing tools such as normalization,slicing,cropping,and augmentation to prepare images for artificial intelligence-based models.It also provides an overview of global herbal image databases and the models employed for herbal plant/drug identification.Readers will gain a comprehensive understanding of the potential application of various machine learning models,including artificial neural networks and convolutional neural networks.The article delves into suitable validation parameters like true positive rates,accuracy,precision,and more for the development of artificial intelligence-based identification and authentication techniques for herbal drugs.This article offers valuable insights and a conclusive platform for the further exploration of artificial intelligence in the field of herbal drugs,paving the way for smarter identification and authentication methods.

Alterations of protein homeostasis in Alzheimer's disease:beyond Procrustean bed of endoplasmic reticulum stress and unfolded protein response

Alzheimer’s disease(AD)is a major age-related form of dementia with a number of cases exponentially growing,causing enormous social and economic impact on individuals and society.Neuropathological hallmarks of AD,evident in postmortem AD brains,include a massive loss of the grey matter in the neocortex,extracellular deposition of amyloid-β(Aβ)in the form of senile plaques and cerebrovascular amyloid angiopathy,and intra-neuronal accumulation of neurofibrillary tangles,formed by hyper-phosphorylated tau protein.

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.

Combination Activity of Standard Antituberculosis Drugs and Extracts of Medicinal Plants Commonly Used in Traditional Treatment of Tuberculosis in Uganda

Introduction: Resistance to antituberculosis drugs and adverse drug reactions remain the leading causes of tuberculosis therapeutic failure globally. Despite the increasing acceptance of medicinal plant use in combination with conventional antituberculosis drugs in treatment of tuberculosis (TB) in Uganda, there is paucity of knowledge on their combination effect. Aim: This research aimed to determine combination activity of standard antituberculosis drugs with extracts of Zanthoxylum leprieurii Guill. & Perr. and Rubia cordifolia L., the two common antituberculosis medicinal plants in Uganda, against pansensitive (H37Rv) and multi-drug resistant (MDR) Mycobacterium tuberculosis strains. Materials and Methods: Two reference MTB strains (H37Rv and MDR strain) were inoculated on Middlebrook 7H11 medium containing a combination of standard antituberculosis drugs and methanol extracts of Z. leprieurii and R. cordifolia at varying concentrations. The number of colonies on the plates was observed and counted weekly for up to 8 weeks. In vitro combination activity was determined using proportion method. Mean percentage inhibition was calculated for the reduction of number of colonies on drug-extract combination medium in relation to drug-extract-free control medium. Results: Drug-extract combinations showed good combination activity against Mycobacterium tuberculosis strains when compared with individual standard anti-TB drugs. This was more exhibited against MDR strain. There was however a reduction in percentage inhibition when extracts were combined with ethambutol and streptomycin against H37Rv strain. Conclusions: Zanthoxylum leprieurii and Rubia cordifolia in combination with standard anti-TB drugs exhibited increased in vitro activity against Mycobacterium tuberculosis, especially MDR-TB strain. This justifies the local use of these plants in traditional treatment of tuberculosis especially in resistant cases in Uganda.

Prevention and treatment of hypoxia-induced colorectal cancer damage in albino Wister rats

Background:In the early metastasis of colon cancer,cancer cells detach,migrate,and infiltrate surrounding tissues,including lymph vessels and blood vessels.Tumor heterogeneity arises from both tumor cells and distinct microenvironments.Maldistribution of blood vessels,creates hypoxic regions within the tumors,fostering cancer stem cell-like properties due to reduced oxygen and nutrient supply.Under hypoxia,tumor cells shift to a glycolytic pathway,producing more lactic acid that acidifies the microenvironment and leads to unstable heart rate variability(HRV)factors,weight disparity,and a higher incidence of aberrant crypt foci(ACF).These hypoxic-induced parameters promote cancer cell invasion,increase radiation resistance,and facilitate cancer cell migration.Methods:In this study,we induced hypoxia-preneoplastic colon damage in albino Wister rats by administrating 1,2-dimethyl hydrazine(DMH).After successfully creating a hypoxic environment in albino Wister rats,resulting in preneoplastic colon damage,we randomly allocated Wistar albino rats into seven groups,each containing 8 animals,and conducted a 6-week study.Group 1-Normal control(administered 1 mM EDTA+saline,2 ml/kg/day,p.o.);group 2-Toxic control(administered DMH,30 mg/kg/week,s.c.);group 3-Standard treatment(DMH,30 mg/kg/week,s.c.for 6 weeks),followed by 5-fluorouracil and Leucovorin(25 mg/kg each on 1^(st),3^(rd),7^(th),and 10^(th) days,i.p.after 6 weeks administration of DMH);group 4-Low dose of P1(DMH,30 mg/kg/week,s.c.+P1,2 mg/kg,i.v.,weekly for 3 weeks);group 5-High dose P1(DMH,30 mg/kg/week,s.c.+P1,4 mg/kg,i.v.,weekly for 3 weeks),group 6-Low dose of P2(DMH,30 mg/kg/week,s.c.,+P2,2 mg/kg,i.v.,weekly for 3 weeks),group 7-High dose of P2(DMH,30 mg/kg/week,s.c.,+P2,4 mg/kg,i.v.weekly for 3 weeks).Results:DMH-treated rats exhibited alterations in HRV factors,weight disparity,elevated gastric pH,increased total acidity,a higher incidence of ACF,and changes in antioxidant markers(TBARs,SOD,catalase,GSH).Brightfield microscopy at 40x magnification revealed the presence of large crypts within aberrant crypt foci in the toxic control group.Conclusion:Treatment groups P1 and P2 containing triazine derivatives initiated proteasomal degradation of Hypoxia Inducible Factor-1α(HIF-1α)by activating Prolyl Hydroxylase(PHDs)pathways.HIF-1αunder a hypoxic environment is responsible for activating a multitude of genes involved in angiogenesis,metastasis,invasiveness,pH changes,metabolic reprogramming,stem cell maintenance,resistance to radiation,and downstream regulation of the immune system.Treatment with P1 and P2 groups helped minimize the ACF count and restored HRV factors,weight disparity,pH levels,total acidity,and oxidative balance.Our findings emphasize the potential role of 1,2,4-triazine derivatives in suppressing hypoxia-induced colon carcinogenesis.

Physicochemical Analysis of Locally Made Yoghurt (Kossam) Commercialised in the City of Douala-Cameroon

Yogurt is a traditional dairy product well known in all the regions of the world. In Cameroon, the most popularly known type is “kossam” also called curdled milk. Kossam is a set of milk based beverage from northern Cameroon presenting great symbolic, economic and social values for local population [1]. 150 Kossam samples were collected from neighborhoods of PK8, Bonamoussadi, Nyalla, cite des palmier, Deido and Bedi community and later on reconstituted into 50 different samples of 350 mL, each containing 1/3 of 3 individual samples. They were analyzed for their physiochemical properties such as: PH, titratable acidity, density, brix and dry matter using most at times the standard Association of Official Analytical Chemists (AOAC) methods with slight modifications and results compared to a licensed brand sold in the Cameroonian market. The results of the study showed that, the physico-chemical properties of the locally made yogurts were different within the different samples. Analysis of variance revealed a significant difference in the levels of the parameters analyzed in the different yogurt samples (p −1 Kg/L), Brix (8˚ - 24˚B), Dornic (23˚ - 160˚D). others contents per 100 g fresh matter are as follows: dry matter (average mean of 16.54%). Hence, the significant variations in the physico-chemical properties of kossam are a call for concern since as it impacts on the health of the population consuming this product.

Efficacy and safety of bamlanivimab in patients with COVID-19:A systematic review and meta-analysis

BACKGROUND Monoclonal antibodies(mAbs)have shown clinical benefits against coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Several studies have reported the use of bamlanivimab as a promising treatment option for COVID-19.AIM To synthesize the latest evidence for the efficacy and safety of bamlanivimab alone in the treatment of adult patients with COVID-19.METHODS A literature search was conducted in PubMed,Cochrane Library,Web of Science,medRxiv,and Google Scholar using“SARS-CoV-2”,“COVID-19”,“LY-CoV555”,and“Bamlanivimab”keywords up to January 25,2023.The quality of included studies was assessed using the Cochrane bias tools.The Comprehensive Meta-Analysis software version 3.0 was used to analyze the data.RESULTS A total of 30 studies involving 47368 patients were included.A significant difference was observed between the bamlanivimab and standard of care/placebo groups in terms of mortality rate[risk ratio(RR)=50,95%confidence interval(CI):0.36-0.70],hospitalization rate(RR=0.51;95%CI:0.39-0.68),and emergency department(ED)visits(RR=0.69;95%CI:0.47-0.99);while the two groups exhibited no significant difference in terms of intensive care unit(ICU)admission(P>0.05).Compared to other mAbs,bamlanivimab was associated with a higher rate of hospitalization(RR=1.44;95%CI:1.07-1.94).However,no significant difference was detected between the bamlanivimab and other mAbs groups in terms of mortality rate,ICU admission,and ED(P>0.05).The incidence of any adverse events was similar between the bamlanivimab and control groups(P>0.05).CONCLUSION Although the results suggest the efficacy and safety of bamlanivimab in COVID-19 patients,further research is required to confirm the efficacy of this drug for the current circulating SARS-CoV-2 variants.

Phytochemical Screening, Study of Acute Toxicity and Hypoglycemic and Antihyperglycemic Activities of Silver Nanoparticles from Guibourtia tessmannii (Harms) J. Leonard (Caesalpiniaceae)

According to the World Health Organization, diabetes affects approximately 347 million people worldwide. Its management is not within the reach of all social classes, therefore medicinal plants are still the first resort for many populations in Africa. The biological material used in this study was the trunk bark of Guibourtia tessmannii. 50 g of trunk bark powder were decocted in 500 ml of distilled water for 5 minutes were carried out. The method used for the synthesis of silver nanoparticles (AgNps) was an organometallic bio-reduction of silver nitrate salts mediated by various secondary metabolites contained in the plant extract. The study of the toxicity acute was conducted according to guideline 423 of the OECD protocol. The pharmacological activities were each carried out with 28 female rats divided into 7 groups of four rats. It was a question for the hypoglycemic activity of administering various doses of silver nanoparticles and other substances to the rats thirty minutes after the carbohydrate intake and for the anti-hyperglycemic activity of administering the same substances to the rats thirty minutes before the carbohydrate intake. The extraction yield was 8.76%. Only the alkaloid test was negative. After acute toxicity study, the LD50 was greater than 2000 mg/kg. Blood sugar tests revealed that glibenclamide 5 mg/kg, which is the reference molecule, lowered blood sugar more than the other treatments applied in the other batches. It was followed by treatment with silver nanoparticles at a dose of 400 μg/kg in both tests. It was therefore concluded that silver nanoparticles from G. tessmannii are good for the formulation of improved traditional medicines and bring up their afficacity .

Kinetic performance comparison of fully and superfcially porous particles with sizes ranging between 2.7 lm and 5 lm: Intrinsic evaluation and application to a pharmaceutical test compound

The reintroduction of superficially porous particles has resulted in a leap forward for the separation performance in liquid chromatography. The underlying reasons for the higher efficiency of columns packed with these particles are discussed. The performance of the newly introduced 5 p.m superficially porous particles is evaluated and compared to 2.7 pm superficially porous and 3.5 and 5 p.m fully porous columns using typical test compounds （alkylphenones） and a relevant pharmaceutical compound （impurity of amoxicillin）. The 5 I.tm superficially porous particles provide a superior kinetic performance compared to both the 3.5 and 5 Ixm fully porous particles over the entire relevant range of separation conditions. The performance of the superficially porous particles, however, appears to depend strongly on retention and analyte properties, emphasizing the importance of comparing different columns under realistic conditions （high enough k） and using the compound of interest.

Probing the degradation of pharmaceuticals in urine using MFC and studying their removal efficiency by UPLC-MS/MS

Nutrient recovery from source-separated human urine has attracted interest as it is rich in nitrogen and phosphorus that can be utilized as fertilizer.However,urine also contains pharmaceuticals,steroid hormones,etc.and their removal is crucial as they have detrimental effects on the environment and human health.The current study focuses on investigating the degradation of pharmaceuticals using a double-chamber microbial fuel cell(MFC).Urine was spiked with four pharmaceuticals(trimethoprim,lamivudine,levofloxacin,and estrone)at a concentration of 2 mg/mL.The MFC was operated for 7 months in batch mode with this spiked urine as feed.The degradation efficiency of the MFC was studied,for which a selective liquid chromatography-tandem mass-spectrometric method was developed for the quantitation of compounds used in the spiking experiments and was validated with a lower limit of quantification of 0.39 ng/mL.The maximum removal rate achieved was 96%±2%.The degradation mechanism involved processes like sorption and anoxic biodegradation.The voltage curve obtained showed that the presence of pharmaceuticals had an initial negative impact on power generation along with increased organic content;however,after the reactor acclimatization,increased power output was achieved with maximum organics removal at 30 h of retention time.This work opens a new perspective for the anoxic biodegradation of pharmaceuticals and can be useful in future bioremediation studies.

Effects of particle size on the triboelectrification phenomenon in pharmaceutical excipients:Experiments and multi-scale modeling

Particle sizes play a major role to mediate charge transfer, both between identical and different material surfaces. The study probes into the probable mechanism that actuates opposite polarities between two different size fractions of the same material by analyzing the charge transfer patterns of two different sizes of microcrystalline cellulose(MCC). Quantum scale calculations confirmed alteration of charge transfer capacities due to variation of moisture content predicted by multiple surface and bulk analytical techniques. Discrete Element Method(DEM) based multi-scale computational models pertinent to predict charge transfer capacities were further implemented, and the results were in accordance to the experimental charge profiles.

Emerging roles of astrocytes in blood-brain barrier disruption upon amyloid-beta insults in Alzheimer's disease

Blood-brain barrier disruption occurs in the early stages of Alzheimer’s disease.Recent studies indicate a link between blood-brain barrier dysfunction and cognitive decline and might accelerate Alzheimer’s disease progression.Astrocytes are the most abundant glial cells in the central nervous system with important roles in the structural and functional maintenance of the blood-brain barrier.For example,astrocytic cove rage around endothelial cells with perivascular endfeet and secretion of homeostatic soluble factors are two major underlying mechanisms of astrocytic physiological functions.Astrocyte activation is often observed in Alzheimer’s disease patients,with astrocytes expressing a high level of glial fibrillary acid protein detected around amyloid-beta plaque with the elevated phagocytic ability for amyloid-beta.Structural alte rations in Alzheimer’s disease astrocytes including swollen endfeet,somata shrinkage and possess loss contribute to disruption in vascular integrity at capillary and arte rioles levels.In addition,Alzheimer’s disease astrocytes are skewed into proinflammatory and oxidative profiles with increased secretions of vasoactive mediators inducing endothelial junction disruption and immune cell infiltration.In this review,we summarize the findings of existing literature on the relevance of astrocyte alte ration in response to amyloid pathology in the context of blood-brain barrier dysfunction.First,we briefly describe the physiological roles of astrocytes in blood-brain barrier maintenance.Then,we review the clinical evidence of astrocyte pathology in Alzheimer’s disease patients and the preclinical evidence in animal and cellular models.We further discuss the structural changes of blood-brain barrier that correlates with Alzheimer’s disease astrocyte.Finally,we evaluate the roles of soluble factors secreted by Alzheimer’s disease astrocytes,providing potential molecular mechanisms underlying blood-brain barrier modulation.We conclude with a perspective on investigating the therapeutic potential of targeting astrocytes for blood-brain barrier protection in Alzheimer’s disease.

Therapeutic potential of exosome-based personalized delivery platform in chronic inflammatory diseases

In the inflammatory microenvironment,there are numerous exosomes secreted by immune cells(Macrophages,neutrophils,dendritic cells),mesenchymal stem cells(MSCs)and platelets as intercellular communicators,which participate in the regulation of inflammation by modulating gene expression and releasing anti-inflammatory factors.Due to their good biocompatibility,accurate targeting,low toxicity and immunogenicity,these exosomes are able to selectively deliver therapeutic drugs to the site of inflammation through interactions between their surface-antibody or modified ligand with cell surface receptors.Therefore,the role of exosome-based biomimetic delivery strategies in inflammatory diseases has attracted increasing attention.Here we review current knowledge and techniques for exosome identification,isolation,modification and drug loading.More importantly,we highlight progress in using exosomes to treat chronic inflammatory diseases such as rheumatoid arthritis(RA),osteoarthritis(OA),atherosclerosis(AS),and inflammatory bowel disease(IBD).Finally,we also discuss their potential and challenges as anti-inflammatory drug carriers.

The effect of an adaptation to hypoxia on cardiac tolerance to ischemia/reperfusion

The acute myocardial infarction(AMI)and sudden cardiac death(SCD),both associated with acute cardiac ischemia,are one of the leading causes of adult death in economically developed countries.The development of new approaches for the treatment and prevention of AMI and SCD remains the highest priority for medicine.A study on the cardiovascular effects of chronic hypoxia(CH)may contribute to the development of these methods.Chronic hypoxia exerts both positive and adverse effects.The positive effects are the infarct-reducing,vasoprotective,and antiarrhythmic effects,which can lead to the improvement of cardiac contractility in reperfusion.The adverse effects are pulmonary hypertension and right ventricular hypertrophy.This review presents a comprehensive overview of how CH enhances cardiac tolerance to ischemia/reperfusion.It is an in-depth analysis of the published data on the underlying mechanisms,which can lead to future development of the cardioprotective effect of CH.A better understanding of the CH-activated protective signaling pathways may contribute to new therapeutic approaches in an increase of cardiac tolerance to ischemia/reperfusion.

Antioxidant Activities and Characterization of Polyphenols from Selected Northern Thai Rice Husks: Relation with Seed Attributes

Rice production generates a significant amount of agricultural waste. This study aimed to give results related to the existence of antioxidant phenols in agricultural waste of selected Northern Thai rice varieties. The antioxidant activities, contents of total flavonoids and phenolic compounds in the ethanolic rice husk extract were evaluated. The highest antioxidant activities were found in the variety PES1CMU, with 2,2’-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid and 2,2-diphenyl-1-picrylhydrazyl as 679.66 and 4.16 mmol/(L·g) trolox equivalent, respectively, ferric reducing antioxidant power as 0.87 mmol/(L·g) Fe2+, total phenolic content as 29.90 mmol/(L·g) gallic acid and total flavonoid content as 12.16 mg/g catechin equivalent. Polyphenol compounds were identified mainly by standard polyphenols using the liquid chromatography mass spectrometry, with the highest contents of phytic acid, o-coumaric acid, naringin and kaempferol. The non-glutenous and wetland ecotypes of rice husk samples were the richest in antioxidant activities and polyphenol contents characterized by using principal component analysis. The glutenous rice husk contained higher antioxidant activities than the rest. Interestingly, quercetin is a significant phenolic compound that positively correlated with the overall antioxidant activities of rice husk. This finding will be relevant for future application of rice husk antioxidant components in the production of functional ingredients as well as for the food and pharmaceutical industries.