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,evi...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.展开更多
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 func...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.展开更多
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...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.展开更多
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 ...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.展开更多
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 res...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 .展开更多
The reintroduction of superfcially porous particles has resulted in a leap forward for the separation performance in liquid chromatography.The underlying reasons for the higher effciency of columns packed with these p...The reintroduction of superfcially porous particles has resulted in a leap forward for the separation performance in liquid chromatography.The underlying reasons for the higher effciency of columns packed with these particles are discussed.The performance of the newly introduced5 mm superfcially porous particles is evaluated and compared to 2.7 mm superfcially porous and3.5 and 5 mm fully porous columns using typical test compounds(alkylphenones)and a relevant pharmaceutical compound(impurity of amoxicillin).The 5 mm superfcially porous particles provide a superior kinetic performance compared to both the 3.5 and 5 mm fully porous particles over the entire relevant range of separation conditions.The performance of the superfcially 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.展开更多
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.a...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.展开更多
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 ...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.展开更多
Many anticancer drugs have an impaired bioavailability and poor brain penetration because they are substrates to drug efflux pumps such as P-glycoprotein and Breast Cancer Resistance Protein.Elacridar is a strong inhi...Many anticancer drugs have an impaired bioavailability and poor brain penetration because they are substrates to drug efflux pumps such as P-glycoprotein and Breast Cancer Resistance Protein.Elacridar is a strong inhibitor of these two drug efflux pumps and therefore has great potential to improve oral absorption and brain penetration of many anticancer drugs.Currently,a clinical formulation of elacridar is unavailable and therefore the pharmaceutical development of a drug product is highly warranted.This also necessitates the availability of an analytical method for its quality control.A reverse-phase high-performance liquid chromatographic method with ultraviolet detection was developed for the pharmaceutical quality control of products containing elacridar as the active pharmaceutical ingredient.The analytical method was validated for linearity,accuracy,precision,selectivity,carry-over,stability of stock and reference solutions,stability of the final extract,stability-indicating capability and impurity testing.We found that elacridar is unstable in aqueous solutions that are exposed to light because a hydroxylation product of elacridar is formed.Therefore,sample solutions with elacridar must be protected from light.展开更多
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...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.展开更多
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. Th...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.展开更多
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 app...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.展开更多
In the United States,schools offer special education services to children who are diagnosed with a learning or neurodevelopmental disorder and have difficulty meeting their learning goals.Pediatricians may play a key ...In the United States,schools offer special education services to children who are diagnosed with a learning or neurodevelopmental disorder and have difficulty meeting their learning goals.Pediatricians may play a key role in helping children access special education services.The number of children ages 6-21 in the United States receiving special education services increased 10.4%from 2006 to 2021.Children receiving special education services under the autism category increased 242%during the same period.The demand for special education services for children under the developmental delay and other health impaired categories increased by 184%and 83%respectively.Although student enrollment in American schools has remained stable since 2006,the percentage distribution of children receiving special education services nearly tripled for the autism category and quadrupled for the developmental delay category by 2021.Allowable heavy metal residues remain persistent in the American food supply due to food ingredient manufacturing processes.Numerous clinical trial data indicate heavy metal exposures and poor diet are the primary epigenetic factors responsible for the autism and attention deficit hyperactivity disorder epidemics.Dietary heavy metal exposures,especially inorganic mercury and lead may impact gene behavior across generations.In 2021,the United States Congress found heavy metal residues problematic in the American food supply but took no legislative action.Mandatory health warning labels on select foods may be the only way to reduce dietary heavy metal exposures and improve child learning across generations.展开更多
Nuclear safety is a global growing concern,where ionizing radiation(IR)is a major injury factor resulting in serious damage to organisms.The detection of IR is usually conducted with physical dosimeters;however,biolog...Nuclear safety is a global growing concern,where ionizing radiation(IR)is a major injury factor resulting in serious damage to organisms.The detection of IR is usually conducted with physical dosimeters;however,biological IR detection methods are deficient.Here,a living composite hydrogel consisting of engineered bacteria and gelatin/sodium alginate was 3D-printed for the biological detection of IR.Three strains of PrecA::egfp gene circuit-containing engineered Escherichia coli were constructed with IR-dependent fluorescence,and the DH5αstrain was finally selected due to its highest radiation response and fluorescence.Engineered bacteria were loaded in a series of gelatin/sodium alginate matrix hydrogels with different rheology,3D printability and bacterial applicability.A high-gelatin-content hydrogel containing 10%gelatin/1.25%sodium alginatewas optimal.The optimal living composite hydrogelwas 3D-printedwith the special bioink,which reported significant green fluorescence underγ-ray radiation.The living composite hydrogel provides a biological strategy for the detection of environmental ionizing radiation.展开更多
Objective:To examine the effects of hydroalcoholic extract and fractions of Hordeum vulgare Linn.(H.vulgare,Da Mai)on streptozotocin(STZ)-induced diabetic nephropathy in Sprague-Dawley rat models.Methods:The study inv...Objective:To examine the effects of hydroalcoholic extract and fractions of Hordeum vulgare Linn.(H.vulgare,Da Mai)on streptozotocin(STZ)-induced diabetic nephropathy in Sprague-Dawley rat models.Methods:The study involved preliminary phytochemical screening of extract and fractions,estimation of secondary metabolites,chromatographic studies using high performance liquid chromatography(HPLC),antioxidant potential using 1,1-diphenyl-2-picrylhydrazyl(DPPH),nitric oxide radical scavenging and reducing power methods along with the determination of potential against diabetic nephropathy in STZ-induced rat models.Results:The phytochemical evaluation of the hydroalcoholic extract of H.vulgare and fractions revealed the presence of various phytoconstituents such as alkaloids,saponins,tannins,flavonoids,and glycosides.The chromatographic analysis indicated the peak complementing marker compound epicatechin and significant antioxidant activity in the extract and aqueous fraction.STZ-induced rats showed abnormal levels of serum albumin,creatinine,total cholesterol,blood urea nitrogen(BUN),and triglycerides,and urine albumin and creatinine,which returned to normal after 8 weeks of treatment with hydroalcoholic extract(400 mg/kg)and aqueous fraction(50 mg/kg)of H.vulgare.Conclusion:Hydroalcoholic extract(400 mg/kg)and aqueous fraction(50 mg/kg)of H.vulgare have significant antioxidant potential and positive effects on diabetic nephropathy.The fractionation and optimization increase the concentration of polyphenols in aqueous extract,causing a decrease in the dose required for effects against diabetic nephropathy.展开更多
Overlook of chiral consideration in transdermal drug delivery increases administrated dose and risk of side effects,decreasing therapeutical effects.To improve the transdermal delivery efficiency of eutomer,this work ...Overlook of chiral consideration in transdermal drug delivery increases administrated dose and risk of side effects,decreasing therapeutical effects.To improve the transdermal delivery efficiency of eutomer,this work focused on investigating the law and mechanism of enantioselective enhancing effects of chiral permeation enhancers on drug enantiomers.Chiral nonsteroidal anti-inflammatory drugs and terpene permeation enhancers were selected as model drug and enhancers.The results indicated that the L-isomer of permeation enhancers increased the skin absorption of S-enantiomer of drug and D-isomer improve the permeation of R-enantiomer,in which the enhancement effect(ER)of Lmenthol on S-enantiomer(ER=3.23)was higher than that on R-enantiomer(ER=1.49).According to the pharmacokinetics results,L-menthol tended to enhance the permeation of S-enantiomer better than R-enantiomer(2.56 fold),and showed excellent in vitro/in vivo correlations.The mechanism study showed that L-isomer of permeation enhancers improved the permeation of S-enantiomer by increasing the retention,but the D-isomer by improving partition for better permeation.Enantioselective mechanism indicated that the weaker chiral H-bond interaction between drug-chiral enhancers was caused by the enantiomeric conformation.Additionally,stronger chiral enhancers-skin interaction between L-isomer and S-conformation of ceramide produced better enhancing effects.In conclusion,enantioselective interaction of chiral drug-chiral enhancers and chiral enhancers-chiral skin played a critical role in transdermal drug delivery,rational utilization of which contributed to improving the uptake of eutomer and inhibiting distomers to decrease a half of dose and side effects,increasing transdermal therapeutical efficiency.展开更多
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 partici...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.展开更多
Morphological hallmarks of axonal degeneration(AxD):Axons transmit signals from one neuron to another and a re crucial for the proper communication in the nervous system.Therefore,the disintegration of axons,a process...Morphological hallmarks of axonal degeneration(AxD):Axons transmit signals from one neuron to another and a re crucial for the proper communication in the nervous system.Therefore,the disintegration of axons,a process named AxD,has detrimental consequences and plays a key role in many neurological diseases.展开更多
Discovering potent drug candidates requires new antimalarial targets.For this reason,antimalarial drug researchers focus on developing new drug candidates on promising targets.In the identification of these targets,a ...Discovering potent drug candidates requires new antimalarial targets.For this reason,antimalarial drug researchers focus on developing new drug candidates on promising targets.In the identification of these targets,a basic understanding of the metabolism and biochemical processes of malaria parasites such as Plasmodium falciparum can prove invaluable.However,malarial resistant parasites are becoming more and more significant issues as antimalarial medications progress.Antimalarial drugs are becoming increasingly resistant,thus the search for new molecules is very important task.Artemisinin based combination therapies are becoming more popular for treating malaria.This will ultimately lead to the selection of resistance due to their extensive and indiscriminate deployment.Alternative artemisinin-based combination therapies are therefore required.There is an interest in finding suitable antimalarial compounds based on their potential effectiveness against malaria.The potential activity of 1,3,4 oxadiazole analogues against malarial infections is a major draw of the search for suitable antimalarial compounds.This review identifies existing antimalarial drugs that have own therapeutic effects and evaluating their feasibility for developing novel synthetic antimalarial derivatives.展开更多
Huntington’s disease (HD)(OMIM 143100) is an autosomal dominant neurodegenerative disorder caused by a monogenic mutation in the huntingtin gene (HTT),which induces typical midlife onset and age-dependent progression...Huntington’s disease (HD)(OMIM 143100) is an autosomal dominant neurodegenerative disorder caused by a monogenic mutation in the huntingtin gene (HTT),which induces typical midlife onset and age-dependent progression with major symptoms including choreic movements,psychiatric disorders,and cognitive impairment(Gusella et al.,2021).After the 1993 discovery of a pathogenic expansion of the CAG trinucleotide repeat beyond 35 in HTT exon 1 as a causative factor for HD,many animal,mammalian cell and yeast models expressing mutant HTT (mHtt) with abnormal CAG repeats have been created to study CAG repeat-induced toxicity (Naphade et al.,2019;Gusella et al.,2021).展开更多
基金the following financial support grant FAR-2019 to DL from The Universita del Piemonte Orientale。
文摘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.
文摘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.
基金C.Karthikeyan,Indira Gandhi National Tribal University,Lalpur,Amarkantak,Anuppur,Madhya Pradesh,484887,India,for providing the gift sample of 1,2,4-triazine derivatives used for the study.
文摘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.
文摘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.
文摘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 .
基金K.B.is a fellow of the Research Foundation Flanders (FWO Vlaanderen)
文摘The reintroduction of superfcially porous particles has resulted in a leap forward for the separation performance in liquid chromatography.The underlying reasons for the higher effciency of columns packed with these particles are discussed.The performance of the newly introduced5 mm superfcially porous particles is evaluated and compared to 2.7 mm superfcially porous and3.5 and 5 mm fully porous columns using typical test compounds(alkylphenones)and a relevant pharmaceutical compound(impurity of amoxicillin).The 5 mm superfcially porous particles provide a superior kinetic performance compared to both the 3.5 and 5 mm fully porous particles over the entire relevant range of separation conditions.The performance of the superfcially 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.
文摘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.
基金supported by the Science and Technology Development Fund (Macao SAR)(120015/2019/ASC,0023/2020/AFJ,0035/2020/AGJ)the University of Macao Research Grant (MYRG2022-00248-ICMS)(all to MPMH)。
文摘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.
文摘Many anticancer drugs have an impaired bioavailability and poor brain penetration because they are substrates to drug efflux pumps such as P-glycoprotein and Breast Cancer Resistance Protein.Elacridar is a strong inhibitor of these two drug efflux pumps and therefore has great potential to improve oral absorption and brain penetration of many anticancer drugs.Currently,a clinical formulation of elacridar is unavailable and therefore the pharmaceutical development of a drug product is highly warranted.This also necessitates the availability of an analytical method for its quality control.A reverse-phase high-performance liquid chromatographic method with ultraviolet detection was developed for the pharmaceutical quality control of products containing elacridar as the active pharmaceutical ingredient.The analytical method was validated for linearity,accuracy,precision,selectivity,carry-over,stability of stock and reference solutions,stability of the final extract,stability-indicating capability and impurity testing.We found that elacridar is unstable in aqueous solutions that are exposed to light because a hydroxylation product of elacridar is formed.Therefore,sample solutions with elacridar must be protected from light.
文摘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.
基金supported by Fundamental Fund 2022the Office of Research Administration,Chiang Mai University,Thailand。
文摘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.
基金supported by the Russian Science Foundation grant 22-15-00048The section dedicated to the role of kinases in the cardioprotective effect of CH is framed within the framework of state assignments 122020300042-4.
文摘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.
文摘In the United States,schools offer special education services to children who are diagnosed with a learning or neurodevelopmental disorder and have difficulty meeting their learning goals.Pediatricians may play a key role in helping children access special education services.The number of children ages 6-21 in the United States receiving special education services increased 10.4%from 2006 to 2021.Children receiving special education services under the autism category increased 242%during the same period.The demand for special education services for children under the developmental delay and other health impaired categories increased by 184%and 83%respectively.Although student enrollment in American schools has remained stable since 2006,the percentage distribution of children receiving special education services nearly tripled for the autism category and quadrupled for the developmental delay category by 2021.Allowable heavy metal residues remain persistent in the American food supply due to food ingredient manufacturing processes.Numerous clinical trial data indicate heavy metal exposures and poor diet are the primary epigenetic factors responsible for the autism and attention deficit hyperactivity disorder epidemics.Dietary heavy metal exposures,especially inorganic mercury and lead may impact gene behavior across generations.In 2021,the United States Congress found heavy metal residues problematic in the American food supply but took no legislative action.Mandatory health warning labels on select foods may be the only way to reduce dietary heavy metal exposures and improve child learning across generations.
基金supported by the Special Program for Capability Promotion
文摘Nuclear safety is a global growing concern,where ionizing radiation(IR)is a major injury factor resulting in serious damage to organisms.The detection of IR is usually conducted with physical dosimeters;however,biological IR detection methods are deficient.Here,a living composite hydrogel consisting of engineered bacteria and gelatin/sodium alginate was 3D-printed for the biological detection of IR.Three strains of PrecA::egfp gene circuit-containing engineered Escherichia coli were constructed with IR-dependent fluorescence,and the DH5αstrain was finally selected due to its highest radiation response and fluorescence.Engineered bacteria were loaded in a series of gelatin/sodium alginate matrix hydrogels with different rheology,3D printability and bacterial applicability.A high-gelatin-content hydrogel containing 10%gelatin/1.25%sodium alginatewas optimal.The optimal living composite hydrogelwas 3D-printedwith the special bioink,which reported significant green fluorescence underγ-ray radiation.The living composite hydrogel provides a biological strategy for the detection of environmental ionizing radiation.
基金supported by Rashtrsant Tukadoji Maharaj Memorial Fellowship from Rashtrasant Tukadoji Maharaj Nagpur University。
文摘Objective:To examine the effects of hydroalcoholic extract and fractions of Hordeum vulgare Linn.(H.vulgare,Da Mai)on streptozotocin(STZ)-induced diabetic nephropathy in Sprague-Dawley rat models.Methods:The study involved preliminary phytochemical screening of extract and fractions,estimation of secondary metabolites,chromatographic studies using high performance liquid chromatography(HPLC),antioxidant potential using 1,1-diphenyl-2-picrylhydrazyl(DPPH),nitric oxide radical scavenging and reducing power methods along with the determination of potential against diabetic nephropathy in STZ-induced rat models.Results:The phytochemical evaluation of the hydroalcoholic extract of H.vulgare and fractions revealed the presence of various phytoconstituents such as alkaloids,saponins,tannins,flavonoids,and glycosides.The chromatographic analysis indicated the peak complementing marker compound epicatechin and significant antioxidant activity in the extract and aqueous fraction.STZ-induced rats showed abnormal levels of serum albumin,creatinine,total cholesterol,blood urea nitrogen(BUN),and triglycerides,and urine albumin and creatinine,which returned to normal after 8 weeks of treatment with hydroalcoholic extract(400 mg/kg)and aqueous fraction(50 mg/kg)of H.vulgare.Conclusion:Hydroalcoholic extract(400 mg/kg)and aqueous fraction(50 mg/kg)of H.vulgare have significant antioxidant potential and positive effects on diabetic nephropathy.The fractionation and optimization increase the concentration of polyphenols in aqueous extract,causing a decrease in the dose required for effects against diabetic nephropathy.
基金supported by the National Natural Science Foundation of China(Grant No.82273879)
文摘Overlook of chiral consideration in transdermal drug delivery increases administrated dose and risk of side effects,decreasing therapeutical effects.To improve the transdermal delivery efficiency of eutomer,this work focused on investigating the law and mechanism of enantioselective enhancing effects of chiral permeation enhancers on drug enantiomers.Chiral nonsteroidal anti-inflammatory drugs and terpene permeation enhancers were selected as model drug and enhancers.The results indicated that the L-isomer of permeation enhancers increased the skin absorption of S-enantiomer of drug and D-isomer improve the permeation of R-enantiomer,in which the enhancement effect(ER)of Lmenthol on S-enantiomer(ER=3.23)was higher than that on R-enantiomer(ER=1.49).According to the pharmacokinetics results,L-menthol tended to enhance the permeation of S-enantiomer better than R-enantiomer(2.56 fold),and showed excellent in vitro/in vivo correlations.The mechanism study showed that L-isomer of permeation enhancers improved the permeation of S-enantiomer by increasing the retention,but the D-isomer by improving partition for better permeation.Enantioselective mechanism indicated that the weaker chiral H-bond interaction between drug-chiral enhancers was caused by the enantiomeric conformation.Additionally,stronger chiral enhancers-skin interaction between L-isomer and S-conformation of ceramide produced better enhancing effects.In conclusion,enantioselective interaction of chiral drug-chiral enhancers and chiral enhancers-chiral skin played a critical role in transdermal drug delivery,rational utilization of which contributed to improving the uptake of eutomer and inhibiting distomers to decrease a half of dose and side effects,increasing transdermal therapeutical efficiency.
基金by the National Natural Science Foundation of China[grant numbers 82170459,2021]Sichuan Science and Technology Program[grant numbers 2022YFH0007,2022]+2 种基金Sichuan Science and Technology Program[grant numbers 23NSFSC1345,2022]the Key Project of Application and Basic Research of Southwest Medical University[grant numbers 2021ZKZD016,2021]the Special Support Project for Young Talents of Southwest Medical University[grant numbers 2020-2022].
文摘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.
基金funded by the Fraunhofer Society,grant number 600199by Joachim Herz Stiftung,grant number 850022 to MZ。
文摘Morphological hallmarks of axonal degeneration(AxD):Axons transmit signals from one neuron to another and a re crucial for the proper communication in the nervous system.Therefore,the disintegration of axons,a process named AxD,has detrimental consequences and plays a key role in many neurological diseases.
文摘Discovering potent drug candidates requires new antimalarial targets.For this reason,antimalarial drug researchers focus on developing new drug candidates on promising targets.In the identification of these targets,a basic understanding of the metabolism and biochemical processes of malaria parasites such as Plasmodium falciparum can prove invaluable.However,malarial resistant parasites are becoming more and more significant issues as antimalarial medications progress.Antimalarial drugs are becoming increasingly resistant,thus the search for new molecules is very important task.Artemisinin based combination therapies are becoming more popular for treating malaria.This will ultimately lead to the selection of resistance due to their extensive and indiscriminate deployment.Alternative artemisinin-based combination therapies are therefore required.There is an interest in finding suitable antimalarial compounds based on their potential effectiveness against malaria.The potential activity of 1,3,4 oxadiazole analogues against malarial infections is a major draw of the search for suitable antimalarial compounds.This review identifies existing antimalarial drugs that have own therapeutic effects and evaluating their feasibility for developing novel synthetic antimalarial derivatives.
基金National Institute of General Medical Sciences grant (SC1GM1111178)to JX。
文摘Huntington’s disease (HD)(OMIM 143100) is an autosomal dominant neurodegenerative disorder caused by a monogenic mutation in the huntingtin gene (HTT),which induces typical midlife onset and age-dependent progression with major symptoms including choreic movements,psychiatric disorders,and cognitive impairment(Gusella et al.,2021).After the 1993 discovery of a pathogenic expansion of the CAG trinucleotide repeat beyond 35 in HTT exon 1 as a causative factor for HD,many animal,mammalian cell and yeast models expressing mutant HTT (mHtt) with abnormal CAG repeats have been created to study CAG repeat-induced toxicity (Naphade et al.,2019;Gusella et al.,2021).
