Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds

PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective therapies.Since PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion diseases.In this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of action.We argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.

Antioxidant and lipoxygenase inhibitory properties of a novel flavonoid from Pistacia chinensis Bunge and its molecular docking analysis

Background:Pistacia chinensis Bunge has been traditionally used to manage various conditions,including asthma,pain,inflammation,hepatoprotection,and diabetes.The study was conducted to investigate the antioxidant and anti-lipoxygenase(LOX)properties of the isolated compound 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one from Pistacia chinensis.Methods:LOX assay and antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl(DPPH)assay were performed.Molecular docking studies were conducted using a molecular operating environment.Results:The LOX assay revealed significant inhibitory effects at 0.2µM concentration,with an IC50 value of 37.80µM.The antioxidant effect demonstrated dose-dependency across 5 to 100µg/mL concentrations,reaching 93.09%at 100µg/mL,comparable to ascorbic acid’s 95.43%effect.Molecular docking studies highlighted strong interactions with the lipoxygenase enzyme,presenting an excellent docking score of-10.98 kcal/mol.Conclusion:These findings provide valuable insights into Pistacia chinensis’chemical components and biological effects,reinforcing its traditional medicinal applications.

Voices that matter:The impact of patient-reported outcome measures on clinical decision-making

The critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific research.PROMs encapsulate a patient's health status directly from their perspective,encompassing various domains such as symptom severity,functional status,and overall quality of life.By integrating PROMs into routine clinical practice and research,healthcare providers can achieve a more nuanced understanding of patient experiences and tailor treatments accordingly.The deployment of PROMs supports dynamic patient-provider interactions,fostering better patient engagement and adherence to tre-atment plans.Moreover,PROMs are pivotal in clinical settings for monitoring disease progression and treatment efficacy,particularly in chronic and mental health conditions.However,challenges in implementing PROMs include data collection and management,integration into existing health systems,and acceptance by patients and providers.Overcoming these barriers necessitates technological advancements,policy development,and continuous education to enhance the acceptability and effectiveness of PROMs.The paper concludes with recommendations for future research and policy-making aimed at optimizing the use and impact of PROMs across healthcare settings.

Infected aortic and iliac aneurysms:Clinical manifestations in the emergency departments of two hospitals in southern Taiwan,China

BACKGROUND: Accurate diagnosis of infected aortic and iliac aneurysms is often delayed, hampering timely treatment and potentially resulting in a fatal consequence. The aim of this study was to discover useful clinical features that can help physicians to identify these patients.METHODS: We reviewed the discharge notes from two hospitals and identifi ed all patients who had a diagnosis of infected aneurysms of the thoracoabdominal aorta and iliac arteries between July 2009 and December 2013. Eighteen patients, aged from 41 to 93, were reviewed. Only 6 patients were diagnosed accurately in their fi rst visit to our ED.RESULTS: Most patients had at least one underlying illness, and it took 1 to 30(9.9±6.5) days for physicians to diagnose their infected aneurysm. Localized pain and fever were the two most commonly presented symptoms. The majority(92%) of isolated microorganisms were gram-negative bacilli, including Salmonella spp, Klebsiella pneumoniae, and Escherichia coli. Two of the 3 patients who underwent non-operative therapy died, and all of the patients who underwent a combination of medical and operative therapies survived.CONCLUSION: We suggest that physicians liberally use computed tomography scans on patients with unknown causes of pain and inflammatory processes. A combination of surgical and medical treatments is indicated for all patients with infected aortic and iliac aneurysms.

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.

New insights into the therapeutic approaches for the treatment of tauopathies

Tauopathies are a group of neurological disorders,including Alzheimer’s disease and frontotemporal dementia,which involve progressive neurodegeneration,cognitive deficits,and aberrant tau protein accumulation.The development of tauopathies cannot currently be stopped or slowed down by treatment measures.Given the significant contribution of tau burden in primary tauopathies and the strong association between pathogenic tau accumulation and cognitive deficits,there has been a lot of interest in creating therapies that can alleviate tau pathology and render neuroprotective effects.Recently,small molecules,immunotherapies,and gene therapy have been used to reduce the pathological tau burden and prevent neurodegeneration in animal models of tauopathies.However,the major pitfall of the current therapeutic approach is the difficulty of drugs and gene-targeting modalities to cross the blood-brain barrier and their unintended side effects.In this review,the current therapeutic strategies used for tauopathies including the use of oligonucleotide-based gene therapy approaches that have shown a promising result for the treatment of tauopathies and Alzheimer’s disease in preclinical animal models,have been discussed.

An oxygenating colloidal bioink for the engineering of biomimetic tissue constructs

Ensuring a sufficient oxygen supply is pivotal for the success of bioprinting applications since it fosters tissue integration and natural regeneration.Variation in oxygen concentration among diverse tissues necessitates the precise recreation of tissue-specific oxygen levels in imprinted constructs to support the survival of targeted cells.Although oxygen-releasing biomaterials,such as oxygen-generating microparticles(OMPs),have shown promise for enhancing the oxygen supply of microenvironments in injured tissues,whether this approach is scalable for large tissues and whether tissue-specific bioinks with varying OMP concentrations remain printable remain unknown.This study addresses this critical gap by introducing an innovative class of engineered oxygenated bioinks that combine colloidal-based microgels with OMPs.We report that incorporating nanosized calcium peroxide(nCaO_(2))and manganese oxide nanosheets(nMnO_(2))into hydrophobic polymeric microparticles enables precise modulation of oxygen release while controlling hydrogen peroxide release.Moreover,the fabrication of oxygenating and cytocompatible colloidal gels is achieved using an aqueous two-phase system.This study thoroughly evaluates the fundamental characteristics of the resulting bioink,including its rheological behaviors,printability,shape fidelity,mechanical properties,and oxygen release properties.Moreover,this study demonstrates the macroscopic scalability and cytocompatibility of printed constructs produced via cell-laden oxygenating colloidal bioinks.By showcasing the effectiveness of extrusion-based bioprinting,this study underscores how it can be used to fabricate biomimetic tissues,indicating its potential for new applications.The findings presented here advance the bioprinting field by achieving scalability with both high cell viability and the possibility of mimicking specifically oxygenated tissues.This work thereby offers a promising avenue for the development of functional tissues with enhanced physiological relevance.

Efficacy of stromal vascular fraction for knee osteoarthritis:A prospective,single-centre,non-randomized study with 2 years follow-up

BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more research is needed for intra-articular stromal vascular fraction(SVF)injections in OA,including dosage optimization,long-term efficacy,safety,comparisons with other treatments,and mechanism exploration.AIM To compare the efficacy of intra-articular SVF with corticosteroid(ICS)injections in patients with primary knee OA.METHODS The study included 50 patients with Kellgren-Lawrence grades II and III OA.Patients were randomly assigned(1:1)to receive either a single intra-articular SVF injection(group A)or a single intra-articular ICS(triamcinolone)(group B)injection.Patients were followed up at 1,3,6,12,and 24 months.Visual analog score(VAS)and International Knee Documentation Committee(IKDC)scores were administered before the procedure and at all followups.The safety of SVF in terms of adverse and severe adverse events was recorded.Statistical analysis was performed with SPSS Version 26.0,IBM Corp,Chicago,IL,United States.RESULTS Both groups had similar demographics and baseline clinical characteristics.Follow-up showed minor patient loss,resulting in 23 and 24 in groups A and B respectively.Group A experienced a notable reduction in pain,with VAS scores decreasing from 7.7 to 2.4 over 24 months,compared to a minor reduction from 7.8 to 6.2 in Group B.This difference in pain reduction in group A was statistically significant from the third month onwards.Additionally,Group A showed significant improvements in knee functionality,with IKDC scores rising from 33.4 to 83.10,whereas Group B saw a modest increase from 36.7 to 45.16.The improvement in Group A was statistically significant from 6 months and maintained through 24 months.CONCLUSION Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA.More adequately powered,multi-center,double-blinded,randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.

Genetics of biochemical attributes regulating morpho-physiology of upland cotton under high temperature conditions

Background Cotton is a strategically important fibre crop for global textile industry.It profoundly impacts several countries’industrial and agricultural sectors.Sustainable cotton production is continuously threatened by the unpre-dictable changes in climate,specifically high temperatures.Breeding heat-tolerant,high-yielding cotton cultivars with wide adaptability to be grown in the regions with rising temperatures is one of the primary objectives of modern cotton breeding programmes.Therefore,the main objective of the current study is to figure out the effective breed-ing approach to imparting heat tolerance as well as the judicious utilization of commercially significant and stress-tolerant attributes in cotton breeding.Initially,the two most notable heat-susceptible(FH-115 and NIAB Kiran)and tolerant(IUB-13 and GH-Mubarak)cotton cultivars were spotted to develop filial and backcross populations to accom-plish the preceding study objectives.The heat tolerant cultivars were screened on the basis of various morphological(seed cotton yield per plant,ginning turnout percentage),physiological(pollen viability,cell membrane thermostabil-ity)and biochemical(peroxidase activity,proline content,hydrogen peroxide content)parameters.Results The results clearly exhibited that heat stress consequently had a detrimental impact on every studied plant trait,as revealed by the ability of crossing and their backcross populations to tolerate high temperatures.However,when considering overall yield,biochemical,and physiological traits,the IUB-13×FH-115 cross went over particularly well at both normal and high temperature conditions.Moreover,overall seed cotton yield per plant exhibited a posi-tive correlation with both pollen viability and antioxidant levels(POD activity and proline content).Conclusions Selection from segregation population and criteria involving pollen viability and antioxidant levels concluded to be an effective strategy for the screening of heat-tolerant cotton germplasms.Therefore,understanding acquired from this study can assist breeders identifying traits that should be prioritized in order to develop climate resilient cotton cultivars.

Constructing a biofunctionalized 3D-printed gelatin/sodium alginate/chitosan tri-polymer complex scaffold with improvised biological andmechanical properties for bone-tissue engineering

Sodium alginate(SA)/chitosan(CH)polyelectrolyte scaffold is a suitable substrate for tissue-engineering application.The present study deals with further improvement in the tensile strength and biological properties of this type of scaffold to make it a potential template for bone-tissue regeneration.We experimented with adding 0%–15%(volume fraction)gelatin(GE),a protein-based biopolymer known to promote cell adhesion,proliferation,and differentiation.The resulting tri-polymer complex was used as bioink to fabricate SA/CH/GEmatrices by three-dimensional(3D)printing.Morphological studies using scanning electron microscopy revealed the microfibrous porous architecture of all the structures,which had a pore size range of 383–419μm.X-ray diffraction and Fourier-transform infrared spectroscopy analyses revealed the amorphous nature of the scaffold and the strong electrostatic interactions among the functional groups of the polymers,thereby forming polyelectrolyte complexes which were found to improve mechanical properties and structural stability.The scaffolds exhibited a desirable degradation rate,controlled swelling,and hydrophilic characteristics which are favorable for bone-tissue engineering.The tensile strength improved from(386±15)to(693±15)kPa due to the increased stiffness of SA/CH scaffolds upon addition of gelatin.The enhanced protein adsorption and in vitro bioactivity(forming an apatite layer)confirmed the ability of the SA/CH/GE scaffold to offer higher cellular adhesion and a bone-like environment to cells during the process of tissue regeneration.In vitro biological evaluation including the MTT assay,confocal microscopy analysis,and alizarin red S assay showed a significant increase in cell attachment,cell viability,and cell proliferation,which further improved biomineralization over the scaffold surface.In addition,SA/CH containing 15%gelatin designated as SA/CH/GE15 showed superior performance to the other fabricated 3D structures,demonstrating its potential for use in bone-tissue engineering.

Influence of edaphic factors on distribution and condition of Himalayan silver birch(Betula utilis D.Don)communities in the northwestern Indian Himalayas

The basic concept of phytosociology is crucial for the assessment of species composition and dynamic ecological succession of forests supporting ecological services,functions,disturbance,and resilience that lead to the development of integrated areas such as ecological niche modeling and contribute to identifying the valuable bio-indicators which can be used in framing conservation and management planning.B.utilis is one of the most dominant tree species of treeline ecotone in the Himalayan Region.The species is also considered as indicator species for monitoring the past and recent climate change impact.The current study was carried out in the natural populations of B.utilis from the sub-alpine zone of North-western Indian Himalaya.The birch dominated forest harbors a total of 305 plant species comprising Angiosperms(51 families,160 genera and 277 species),Gymnosperms(03 families,05 genera and 07 species)and Pteridophytes(07 families,11 genera and 21 species)with Asteraceae,Ranunculaceae and Rosaceae as dominant family.Birch forests are found dominant in shady moist habitat and North West aspect.Geographical characteristics,anthropogenic and developmental activities affect the population structure of B.utilis and associated species.However,the species has fair regeneration status in the study area.The acidic nature of soil pH and spatial variation in edaphic characteristics may be due to geographical differences,rooting patterns and litter accumulation of below and above-ground vegetation.Biomass estimation of a representative population of B.utilis from each site showed that TAGBD,TCD and TBD were found maximum in ST3(Hamta Pass II site).The CCA analysis determined that environmental variables such as altitude,organic matter,available phosphorous,organic carbon,available nitrogen,and electrical conductivity played a significant role in determining tree species composition and distribution in B.utilis dominated forests.

Bulked Segregant RNA-Seq Analysis of Pollinated Pistils Reveals Genes Influencing Spikelet Fertility in Rice

Prezygotic isolation is important for successful fertilization in rice, significantly affecting yield. This study focused on F_(5:6) generation plants derived from inter-subspecific crosses(Nipponbare × KDML105) with low(LS) and high seed-setting rates(HS), in which normal pollen fertility was observed. However, LS plants showed a reduced number of pollen grains adhering to the stigma and fewer pollen tubes reaching the ovules at 4-5 h post-pollination, compared with HS plants. Bulked segregant RNA-Seq analysis of pollinated pistils from the HS and LS groups revealed 249 and 473 differentially expressed genes(DEGs), respectively. Kyoto Encyclopedia of Genes and Genomes analysis of the HS and LS-specific DEGs indicated enrichment in metabolic pathways, pentose and glucuronate interconversions, and flavonoid biosynthesis. Several of these DEGs exhibited co-expression with pollen development genes and formed extensive clusters of co-expression networks. Compared with LS pistils, enzyme genes controlling pectin degradation, such as OsPME35 and OsPLL9, showed similar expression patterns, with higher levels in HS pistils pre-pollination. Os02g0467600, similar to cinnamate 4-hydroxylase gene(CYP73), involved in flavonoid biosynthesis, displayed higher expression in HS pistils post-pollination. Our findings suggest that OsPME35, OsPLL9, and Os02g0467600 contribute to prezygotic isolation by potentially modifying the stigma cell wall(OsPME35 and OsPLL9) and controlling later processes such as pollen-stigma adhesion(Os02g0467600) genes. Furthermore, several DEGs specific to HS and LS were co-localized with QTLs and functional genes associated with spikelet fertility. These findings provide valuable insights for further research on rice spikelet fertility, ultimately contributing to the development of high-yielding rice varieties.

Combined Insights from Leachate Structure and Microstructure Characteristics for Eating Quality of Convenience Rice Processed by Super-Heated and Pressurized Steam Technologies

Convenience rice has become widely popular due to its easy availability for cooking. This study investigated the starch structure and composition of leachate and the microstructure of reheated convenience rice using novel processing technologies: super-heated steaming(SHS), auto-electric cooking(AEC), and pressurized-steam cooking(PSC). Additionally, the effect of two different target water contents(58% and 63%) was also evaluated. The PSC_63% sample had the highest total solids and amylopectin amount in the leachate. The amylopectin amount in the leachate differed significantly based on the targeted water content. Morphological characterization revealed that the swelling of starch and the coated layer on the surface of rice grains were most pronounced in the PSC_63% sample due to the pressure processing. The textural hardness of the AEC_58% sample was much higher than that of the other samples. The PSC_63% sample had the highest textural adhesiveness value, which can be attributed to the highest amylopectin amount in the leachate. Sensory characterization showed that the PSC_63% sample had the highest glossiness, whiteness, moistness, and overall acceptability. The principal component analysis score plots presented substantial differences in the leachate and textural and sensory characteristics of reheated convenience rice among the different processing technologies.

Structural analysis of silk using solid-state NMR

Silkworms and spiders are capable of generating fibers that are both highly durable and elastic in a short span of time,using a silk solution stored within their bodies at room temperature and normal atmospheric pressure.The dragline silk fiber,which is essentially a spider's lifeline,surpasses the strength of a steel wire of equivalent thickness.Regrettably,humans have yet to replicate this process to produce fibers with similar high strength and elasticity in an eco-friendly manner.Therefore,it is of utmost importance to thoroughly comprehend the extraordinary structure and fibrillation mechanism of silk,and leverage this understanding in the manufacturing of high-strength,high-elasticity fibers.This review will delve into the recent progress in comprehending the structure of silks derived from silkworms and spiders,emphasizing the distinctive attributes of solidstate NMR.

Effects of low molecular weight polysaccharide from Sargassum thunbergii against palmitic acid-induced intracellular lipid accumulation in 3T3-L1 adipocyte and HepG2 cells

Low molecular weight polysaccharides can be isolated from Sargassum thunbergii(LMPST)and in vitro experiments were conducted to evaluate the inhibitory effects on lipids.Two natures of LMPST were attained from S.thunbergii and appraised their LMPST on palmitic acid(PA)induced lipid accretion in Hep G2,and 3T3-L1 cells.LMPST treatment lessened lipid deposition and intracellular free fatty acid and triglyceride intensities in PA-treated above mentioned cells.The mechanistic study publicized that LMPST2 significantly suppressed adipogenesis and stimulated the PA-treated 3T3-L1 cells occupied in the lipolysis pathway.Furthermore,in PA-treated Hep G2 cells,the free fatty acid oxidation was significantly increased by LMPST2.Given these constructive properties of LMPST2 from S.thunbergii,is a potential candidate for diminishing the intracellular lipids,and for a therapeutic agent in those conditions.

Genome-wide identification and expression profiling of photosystem II(PsbX)gene family in upland cotton(Gossypium hirsutum L.)

Background Photosystem II(PSII)constitutes an intricate assembly of protein pigments,featuring extrinsic and intrinsic polypeptides within the photosynthetic membrane.The low-molecular-weight transmembrane protein PsbX has been identified in PSII,which is associated with the oxygen-evolving complex.The expression of PsbX gene protein is regulated by light.PsbX’s central role involves the regulation of PSII,facilitating the binding of quinone molecules to the Qb(PsbA)site,and it additionally plays a crucial role in optimizing the efficiency of photosynthesis.Despite these insights,a comprehensive understanding of the PsbX gene’s functions has remained elusive.Results In this study,we identified ten PsbX genes in Gossypium hirsutum L.The phylogenetic analysis results showed that 40 genes from nine species were classified into one clade.The resulting sequence logos exhibited substantial conservation across the N and C terminals at multiple sites among all Gossypium species.Furthermore,the ortholo-gous/paralogous,Ka/Ks ratio revealed that cotton PsbX genes subjected to positive as well as purifying selection pressure might lead to limited divergence,which resulted in the whole genome and segmental duplication.The expression patterns of GhPsbX genes exhibited variations across specific tissues,as indicated by the analysis.Moreover,the expression of GhPsbX genes could potentially be regulated in response to salt,intense light,and drought stresses.Therefore,GhPsbX genes may play a significant role in the modulation of photosynthesis under adverse abiotic conditions.Conclusion We examined the structure and function of PsbX gene family very first by using comparative genom-ics and systems biology approaches in cotton.It seems that PsbX gene family plays a vital role during the growth and development of cotton under stress conditions.Collectively,the results of this study provide basic information to unveil the molecular and physiological function of PsbX genes of cotton plants.

Characterization of early maturing elite genotypes based on MTSI and MGIDI indexes:an illustration in upland cotton(Gossypium hirsutum L.)

Background Globally,the cultivation of cotton is constrained by its tendency for extended periods of growth.Early maturity plays a potential role in rainfed-based multiple cropping system especially in the current era of climate change.In the current study,a set of 20 diverse Gossypium hirsutum genotypes were evaluated in two crop seasons with three planting densities and assessed for 11 morphological traits related to early maturity.The study aimed to identify genotype(s)that mature rapidly and accomplish well under diverse environmental conditions based on the two robust multivariate techniques called multi-trait stability index(MTSI)and multi-trait genotype-ideotype distance index(MGIDI).Results MTSI analysis revealed that out of the 20 genotypes,three genotypes,viz.,NNDC-30,A-2,and S-32 accomplished well in terms of early maturity traits in two seasons.Furthermore,three genotypes were selected using MGIDI method for each planting densities with a selection intensity of 15%.The strengths and weaknesses of the genotypes selected based on MGIDI method highlighted that the breeders could focus on developing early-maturing genotypes with specific traits such as days to first flower and boll opening.The selected genotypes exhibited positive genetic gains for traits related to earliness and a successful harvest during the first and second pickings.However,there were negative gains for traits related to flowering and boll opening.Conclusion The study identified three genotypes exhibiting early maturity and accomplished well under different planting densities.The multivariate methods(MTSI and MGIDI)serve as novel approaches for selecting desired genotypes in plant breeding programs,especially across various growing environments.These methods offer exclusive benefits and can easily construe and minimize multicollinearity issues.

Creep properties of bimetal Al/SiC/Cu compositesfabricated via accumulative roll bonding process

In the present study,microstructural evolution,mechanical and creep properties of Al/SiC/Cu composite stripsfabricated via accumulative roll bonding(ARB)process were studied.The obtained results showed the formation of anatomic diffusion layer with thickness of about 17μm at the interface during the ARB under three creep loadingconditions namely 30 MPa at 225℃,35 MPa at 225℃,and 35 MPa at 275℃.An generated intermetallic compoundresulted in a 40%increase of interface thickness near Al.The stress level decreased by 13%at constant temperature withno signi fi cant effect on the interface thickness,and the creep failure time declined by 44%.It was observed that atconstant temperatures,the second slope of the creep curve reached to 39%with increasing stress level,then,it dropped to2%with a little temperature rising.After creep test under 35 MPa at 275℃,the sample displays the presence of 60%Aland 40%Cu,containing brittle Al_(2)Cu intermetallic compound at the interface.Applied temperature and stress had effecton the creep properties,specially increasing the slope of creep curves with higher stresses.

Metabolic complications of psychotropic medications in psychiatric disorders:Emerging role of de novo lipogenesis and therapeutic consideration

Although significant advances have been made in understanding the pathophysiology of psychiatric disorders(PDs),therapeutic advances have not been very convincing.While psychotropic medications can reduce classical symptoms in patients with PDs,their long-term use has been reported to induce or exaggerate various pre-existing metabolic abnormalities including diabetes,obesity and non-alcoholic fatty liver disease(NAFLD).The mechanism(s)underlying these metabolic abnormalities is not clear;however,lipid/fatty acid accumulation due to enhanced de novo lipogenesis(DNL)has been shown to reduce membrane fluidity,increase oxidative stress and inflammation leading to the development of the aforementioned metabolic abnormalities.Intriguingly,emerging evidence suggest that DNL dysregulation and fatty acid accumulation could be the major mechanisms associated with the development of obesity,diabetes and NAFLD after long-term treatment with psychotropic medications in patients with PDs.In support of this,several adjunctive drugs comprising of anti-oxidants and antiinflammatory agents,that are used in treating PDs in combination with psychotropic medications,have been shown to reduce insulin resistance and development of NAFLD.In conclusion,the above evidence suggests that DNL could be a potential pathological factor associated with various metabolic abnormalities,and a new avenue for translational research and therapeutic drug designing in PDs.

Tenosynovitis of hand: Causes and complications

Tenosynovitis represents a common clinical condition characterized by inflam-mation of the synovium that encases the tendon sheath.Although tenosynovities may be noted in any tendon in the body,extremities such as hand,and foot remain the sites of high predilection to acquire this condition.The predominant cause of this predilection rests in the intricate tendon arrangements in these extremities that permit fine motor actions.This editorial explores the common causes and the complications associated with this condition to improve the understanding of the readers of this common condition encountered in our everyday clinical practice.