Evidence that tirzepatide protects against diabetes-related cardiac damages.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective antidiabetic drugs with potential cardiovascular benefits. Despite their well-established role in reducing the risk of major adverse cardiovascular events (MACE), their impact on heart failure (HF) remains unclear. Therefore, our study examined the cardioprotective effects of tirzepatide (TZT), a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist. METHODS: A three-steps approach was designed: (i) Meta-analysis investigation with the primary objective of assessing major adverse cardiovascular events (MACE) occurrence from major randomized clinical trials.; (ii) TZT effects on a human cardiac AC16 cell line exposed to normal (5 mM) and high (33 mM) glucose concentrations for 7 days. The gene expression and protein levels of primary markers related to cardiac fibrosis, hypertrophy, and calcium modulation were evaluated. (iii) In silico data from bioinformatic analyses for generating an interaction map that delineates the potential mechanism of action of TZT. RESULTS: Meta-analysis showed a reduced risk for MACE events by TZT therapy (HR was 0.59 (95% CI 0.40-0.79, Heterogeneity: r2 = 0.01, I2 = 23.45%, H2 = 1.31). In the human AC16 cardiac cell line treatment with 100 nM TZT contrasted high glucose (HG) levels increase in the expression of markers associated with fibrosis, hypertrophy, and cell death (p < 0.05 for all investigated markers). Bioinformatics analysis confirmed the interaction between the analyzed markers and the associated pathways found in AC16 cells by which TZT affects apoptosis, fibrosis, and contractility, thus reducing the risk of heart failure. CONCLUSION: Our findings indicate that TZT has beneficial effects on cardiac cells by positively modulating cardiomyocyte death, fibrosis, and hypertrophy in the presence of high glucose concentrations. This suggests that TZT may reduce the risk of diabetes-related cardiac damage, highlighting its potential as a therapeutic option for heart failure management clinical trials. Our study strongly supports the rationale behind the clinical trials currently underway, the results of which will be further investigated to gain insights into the cardiovascular safety and efficacy of TZT.

Using ER-Targeted Photoconvertible Fluorescent Proteins in Living Plant Cells.

Photoconvertible fluorescent proteins (pcFPs) enable differential coloring of a single organelle. Several pcFP-based probes have been targeted to the endoplasmic reticulum (ER) and can serve as useful tools to study ER dynamics and interactions with other organelles. Here, we describe the procedure to conduct live-cell imaging experiments using ER-targeted pcFP-based probes. Potential problems that might occur during the experiments, their solutions, and several ways to improve the experiments are discussed.

Tirzepatide prevents neurodegeneration through multiple molecular pathways.

BACKGROUND: Several evidence demonstrated that glucagon-like peptide 1 receptor agonists (GLP1-RAs) reduce the risk of dementia in type 2 diabetes patients by improving memory, learning, and overcoming cognitive impairment. In this study, we elucidated the molecular processes underlying the protective effect of Tirzepatide (TIR), a dual glucose-dependent insulinotropic polypeptide receptor agonist (GIP-RA)/ GLP-1RA, against learning and memory disorders. METHODS: We investigated the effects of TIR on markers of neuronal growth (CREB and BDNF), apoptosis (BAX/Bcl2 ratio) differentiation (pAkt, MAP2, GAP43, and AGBL4), and insulin resistance (GLUT1, GLUT4, GLUT3 and SORBS1) in a neuroblastoma cell line (SHSY5Y) exposed to normal and high glucose concentration. The potential role on DNA methylation of genes involved in neuroprotection and epigenetic modulators of neuronal growth (miRNA 34a), apoptosis (miRNA 212), and differentiation (miRNA 29c) was also investigated. The cell proliferation was detected by measuring Ki-67 through flow cytometry. The data were analysed by SPSS IBM Version 23 or GraphPad Prism 7.0 software and expressed as the means ± SEM. Differences between the mean values were considered significant at a p-value of < 0.05. GraphPad Prism software was used for drawing figures. RESULTS: For the first time, it was highlighted: (a) the role of TIR in the activation of the pAkt/CREB/BDNF pathway and the downstream signaling cascade; (b) TIR efficacy in neuroprotection; (c) TIR counteracting of hyperglycemia and insulin resistance-related effects at the neuronal level. CONCLUSIONS: We demonstrated that TIR can ameliorate high glucose-induced neurodegeneration and overcome neuronal insulin resistance. Thus, this study provides new insight into the potential role of TIR in improving diabetes-related neuropathy.

Reversal mechanism of multidrug-resistant cancer cells by lectin as chemo-adjuvant and targeted therapy- a systematic review.

BACKGROUND: Cancer is characterized as the leading cause of death, and the susceptibility of cancer cells to develop resistance due to long-term exposure to complementary chemotherapeutic treatment is referred to as multidrug resistance cancer cells (MDRC), which is a significant obstacle in the treatment of malignancies. Since complementary medicine lost its effectiveness, the development of potential alternative and novel therapeutic approaches has been elevated to a top priority in recent years. In this context, a bioactive protein lectin from plant and animal sources exhibits an invaluable source of anticancer agents with vast therapeutic potential. PURPOSE: This manuscript's primary purpose is to enlighten the evidence-based (from 1986 to 2022) possible molecular mechanism of alternative treatment approaches using lectins over the complementary medicines used for cancer treatment. METHODS: The PRISMA rules have been followed properly and qualitative and quantitative data are synthesized systematically. Articles were identified based on Clinical and preclinical reports published on lectin that investigated the in-depth cellular mechanisms, of reverse drug integrative oncology, as a nano-carried targeted delivery. Articles were systematically screened from 1986 to 2022 and selected based on electronic database searches, Medline (PubMed), Google Scholar, Web of Science, Encyclopaedias, Scopus, and ClinicalTrials.gov database. RESULTS: The search turned up 4,212 publications from 38 different nations, of which 170 reference articles were used in our analysis, in 16 combination therapy and their mode of action, and 27 clinical trial studies including dosage and mechanism of action were included. Reports from the 30 lectins belonging to 28 different families have been included. The reversal mechanism of lectin and alternative therapy against MDRC is critically screened and according to a few clinical and preclinical reports, lectin can suppress the overexpressing genes like P-53, EGFR, and P-gp, MRP, and ABC transporter proteins associated with intracellular transportation of drugs. Since, the drug efflux mechanism leads to MDRC, in this phenomenon, lectin plays a key role in reversing the efflux mechanism. Few preclinical reports have mentioned that lectin shows synergism in combination with complementary medicine and as a nano drug carrier helps to deliver to the targeted site. CONCLUSION: We have discussed the alternative therapy using lectin and an in-depth insight into the reversal drug resistance mechanisms to combat MDRC cancer, enhance the efficacy, reduce toxicity and adverse events, and ensure targeted delivery, and their application in the field of cancer diagnosis and prognosis has been discussed. However, further investigation is necessary in drug development and clinical trials which could be helpful to elaborate the reversal mechanism and unlock newer treatment modalities in MDRC cancer.

Jackfruit waste: an invented anticancer therapy using Jacalin lectin from jackfruit seed.

Every food source contains both edible and inedible waste components. Millions of tonnes of trash from the food business are made from fruits, and these wastes are containing higher-value medicinal components, such as alkaloids, flavonoids, phenolic contents, a huge amount of proteins and secondary metabolites. These bioactive phytoconstituents are being used for the treatment of many serious fatal diseases. So, utilizing the recovered bioactive molecules from food wastes as functional ingredients offers a long-term alternative source of therapeutically active components that will lead to the discovery of novel phytoconstituents or novel treatment approaches. The goal of this systematic study is to provide an overview of the jackfruit (Artocarpus heterophyllus Lam, Moraceae) edible byproducts, such as jackfruit seeds that are largely neglected. This seed contains numerous bioactive lead molecules, such as carbohydrate-binding protein jacalin, which exhibits potent anticancer activity against colon cancer, blood cancer and breast cancer as well as can enlighten the new possible treatment approaches in targeted therapy and photodynamic chemotherapy. Moreover, jackfruit waste seed can be taken as a dietary food, which is having property to prevent and treat cancer and other lifestyle diseases. The works that have been carried out to utilize jackfruit waste other than the juicy edible bulbs have been reviewed in this article.

Structural analysis of novel drug targets for mitigation of Pseudomonas aeruginosa biofilms.

Pseudomonas aeruginosa is an opportunistic human pathogen responsible for acute and chronic, hard to treat infections. Persistence of P. aeruginosa is due to its ability to develop into biofilms, which are sessile bacterial communities adhered to substratum and encapsulated in layers of self-produced exopolysaccharides. These biofilms provide enhanced protection from the host immune system and resilience towards antibiotics, which poses a challenge for treatment. Various strategies have been expended for combating biofilms, which involve inhibiting biofilm formation or promoting their dispersal. The current remediation approaches offer some hope for clinical usage, however, treatment and eradication of preformed biofilms is still a challenge. Thus, identifying novel targets and understanding the detailed mechanism of biofilm regulation becomes imperative. Structure-based drug discovery (SBDD) provides a powerful tool that exploits the knowledge of atomic resolution details of the targets to search for high affinity ligands. This review describes the available structural information on the putative target protein structures that can be utilized for high throughput in silico drug discovery against P. aeruginosa biofilms. Integrating available structural information on the target proteins in readily accessible format will accelerate the process of drug discovery.

Targeting redox imbalance in neurodegeneration: characterizing the role of GLP-1 receptor agonists.

Reactive oxygen species (ROS) have emerged as essential signaling molecules regulating cell survival, death, inflammation, differentiation, growth, and immune response. Environmental factors, genetic factors, or many pathological condition such as diabetes increase the level of ROS generation by elevating the production of advanced glycation end products, reducing free radical scavengers, increasing mitochondrial oxidative stress, and by interfering with DAG-PKC-NADPH oxidase and xanthine oxidase pathways. Oxidative stress, and therefore the accumulation of intracellular ROS, determines the deregulation of several proteins and caspases, damages DNA and RNA, and interferes with normal neuronal function. Furthermore, ROS play an essential role in the polymerization, phosphorylation, and aggregation of tau and amyloid-beta, key mediators of cognitive function decline. At the neuronal level, ROS interfere with the DNA methylation pattern and various apoptotic factors related to cell death, promoting neurodegeneration. Only few drugs are able to quench ROS production in neurons. The cross-linking pathways between diabetes and dementia suggest that antidiabetic medications can potentially treat dementia. Among antidiabetic drugs, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been found to reduce ROS generation and ameliorate mitochondrial function, protein aggregation, neuroinflammation, synaptic plasticity, learning, and memory. The incretin hormone glucagon-like peptide-1 (GLP-1) is produced by the enteroendocrine L cells in the distal intestine after food ingestion. Upon interacting with its receptor (GLP-1R), it regulates blood glucose levels by inducing insulin secretion, inhibiting glucagon production, and slowing gastric emptying. No study has evidenced a specific GLP-1RA pathway that quenches ROS production. Here we summarize the effects of GLP-1RAs against ROS overproduction and discuss the putative efficacy of Exendin-4, Lixisenatide, and Liraglutide in treating dementia by decreasing ROS.

Nature-Driven Biocompatible Epidermal Electronic Skin for Real-Time Wireless Monitoring of Human Physiological Signals.

Wearable bioelectronic patches are creating a transformative effect in the health care industry for human physiological signal monitoring. However, the use of such patches is restricted due to the unavailability of a proper power source. Ideal biodevices should be thin, soft, robust, energy-efficient, and biocompatible. Here, we report development of a flexible, lightweight, and biocompatible electronic skin-cum-portable power source for wearable bioelectronics by using a processed chicken feather fiber. The device is fabricated with a novel, breathable composite of biowaste chicken feather and organic poly(vinylidene fluoride) (PVDF) polymer, where the chicken feather fiber constitutes the "microbones" of the PVDF, enhancing its piezoelectric phase content, biocompatibility, and crystallinity. Thanks to its outstanding pressure sensitivity, the fabricated electronic skin is used for the monitoring of different human physiological signals such as body motion, finger and joint bending, throat activities, and pulse rate with excellent sensitivity. A wireless system is developed to remotely receive the different physiological signals as captured by the electronic skin. We also explore the capabilities of the device as a power source for other small electronics. The piezoelectric energy harvesting device can harvest a maximum output voltage of ∼28 V and an area power density of 1.4 µW·cm-2 from the human finger imparting. The improved energy harvesting property of the device is related to the induced higher fraction of the electroactive phase in the composite. The easy process ability, natural biocompatibility, superior piezoelectric performance, high pressure sensitivity, and alignment toward wireless transmission of the captured data make the device a promising candidate for wearable bioelectronic patches and power sources.

Targeting high glucose-induced epigenetic modifications at cardiac level: the role of SGLT2 and SGLT2 inhibitors.

BACKGROUND: Sodium-glucose co-transporters (SGLT) inhibitors (SGLT2i) showed many beneficial effects at the cardiovascular level. Several mechanisms of action have been identified. However, no data on their capability to act via epigenetic mechanisms were reported. Therefore, this study aimed to investigate the ability of SGLT2 inhibitors (SGLT2i) to induce protective effects at the cardiovascular level by acting on DNA methylation. METHODS: To better clarify this issue, the effects of empagliflozin (EMPA) on hyperglycemia-induced epigenetic modifications were evaluated in human ventricular cardiac myoblasts AC16 exposed to hyperglycemia for 7 days. Therefore, the effects of EMPA on DNA methylation of NF-κB, SOD2, and IL-6 genes in AC16 exposed to high glucose were analyzed by pyrosequencing-based methylation analysis. Modifications of gene expression and DNA methylation of NF-κB and SOD2 were confirmed in response to a transient SGLT2 gene silencing in the same cellular model. Moreover, chromatin immunoprecipitation followed by quantitative PCR was performed to evaluate the occupancy of TET2 across the investigated regions of NF-κB and SOD2 promoters. RESULTS: Seven days of high glucose treatment induced significant demethylation in the promoter regions of NF-kB and SOD2 with a consequent high level in mRNA expression of both genes. The observed DNA demethylation was mediated by increased TET2 expression and binding to the CpGs island in the promoter regions of analyzed genes. Indeed, EMPA prevented the HG-induced demethylation changes by reducing TET2 binding to the investigated promoter region and counteracted the altered gene expression. The transient SGLT2 gene silencing prevented the DNA demethylation observed in promoter regions, thus suggesting a role of SGLT2 as a potential target of the anti-inflammatory and antioxidant effect of EMPA in cardiomyocytes. CONCLUSIONS: In conclusion, our results demonstrated that EMPA, mainly acting on SGLT2, prevented DNA methylation changes induced by high glucose and provided evidence of a new mechanism by which SGLT2i can exert cardio-beneficial effects.

Dissecting the biochemical and molecular-genetic regulation of diverse metabolic pathways governing aroma formation in indigenous aromatic indica rice varieties.

BACKGROUND: Aromatic rice is characterized by its distinct flavor and fragrance, imparted by more than 200 volatile organic compounds. The desirable trait of aroma relies on the type of the variety, with some varieties exhibiting considerably higher aroma content. This prompted us to undergo an exhaustive study of the aroma-associated biochemical pathways and expression of related genes, encoding the enzymes involved in those pathways in indigenous aromatic rice cultivars. METHODS AND RESULTS: The higher aroma level in aromatic rice varieties was attributed to higher transcript levels of PDH, P5CS, OAT, ODC, DAO and TPI, but lower P5CDH and BADH2, as revealed by comparative expression profiling of genes in 11 aromatic and four non-aromatic varieties. Some of the high-aroma containing varieties exhibited lower expression of SPDS and SPMS genes, concomitant with higher PAO expression. Protein immunoblot analyses showed lesser BADH2 protein accumulation in the aromatic varieties. The involvement of shikimate pathway in aroma formation was justified by higher levels of shikimic and ferulic acids due to higher expression of SK1, SK2 and ARD genes. The aromatic varieties exhibited higher expression of LOX3 and HPL, with higher corresponding enzyme activity, accompanied with lower accumulation of lipid hydroperoxides and higher level of total terpenoids, signifying the role of oxylipin pathway and terpene-related volatiles in aroma formation. The pattern of transcript level and metabolite accumulation followed the same trend in both vegetative (seedling) and reproductive (seed) tissues. Sequence analyses revealed several mutations in the upstream region and different exons and introns of BADH2 in the examined aromatic varieties. The allele specific marker system acted as fingerprint to distinguish the selected aromatic rice varieties. The cleaved amplified polymorphic sequence marker established the absence of any mutation in the 14th exon of BADH2 in the aromatic varieties. CONCLUSION: The present work clearly highlighted the biochemical and molecular-genetic mechanism of differential aroma levels which could be attributed to differential regulation of metabolites and genes, belonging to 2-acetyl-1-pyrroline, shikimate, oxylipin and terpenoid metabolic pathways in the indigenous aromatic rice varieties.

Impact of COVID-19 pandemic on surgical residency: Residents' perception.

BACKGROUND: World Health Organization declared COVID-19 outbreak a pandemic, and till the month of March 2023, globally, there have been 761,402,282 confirmed cases of COVID-19, including 6887,000 deaths. In India, almost 44,707,525 cases been recorded till date. Here, almost 30,000,000 cases been recorded after the second wave. The working force fighting this pandemic is majority formed by resident doctors all over the country and globally. MATERIALS AND METHODS: This study was conducted among 110 residents pursuing postgraduation in surgery and allied departments in various training institutions in Tamil Nadu for a duration of 6 months (after the second wave). A pretested and validated questionnaire was formulated to assess the effect of COVID-19 pandemic on surgical trainee's residency program from their perspective. The questionnaire contained basic social-demographic details and general information like the details of surgical specialty they are admitted to, the overall details of changes in their surgical residency experience in the times of COVID pandemic and the changes faced by them in their day-to-day clinical, diagnostic, and surgical learning. The questionnaire also investigated the redeployment status of the surgical trainees to COVID treatment units and their perspective on the changes in their clinical research and surgical skills training. RESULTS: The study participants, 66%, were aged between 25 and 30 years, followed by 30 and 35 years (25.5%). Almost 80% of the participants belong to the final year of postgraduation; 67.3% of surgical trainees strongly perceives and all 100% of them accept the fact that their surgical residency has been affected by the ongoing pandemic. Fifty percent of the trainees were redeployed to COVID duties for 8 h a day shift and rest attended a minimum of 4 h of COVID duties. More than 75% of the residents had COVID duties of 5-10 h/day and more than 90% of these redeployed trainees involved in COVID duties have expressed that they had been suffering from extra stress and more than 60% were suffering from stress grade between 5 and 10 suggestive of high-stress level. Fifty-nine percent of the postgraduates in the current study mentioned that they require extra-surgical or skill-based training after their postgraduation period. CONCLUSION: The influence of COVID-19 on surgical trainees in various institutions of India has been immense due to overburdening of health systems by the large population of the country. Second wave of COVID, especially, has drastically changed the postgraduate surgical trainees' lives. Detrimental effects are not restricted to operative and clinical experience but also the mental health and well-being of them. The observations of the present study make recommendations for the future provision of training through skill-based surgical simulations so that the lost days of their trainings can be compensated and they become the confident surgeons of the future.

Neuroprotective role of coconut oil for the prevention and treatment of Parkinson's disease: potential mechanisms of action.

Neurodegenerative disease (ND) is a clinical condition in which neurons degenerate with a consequent loss of functions in the affected brain region. Parkinson's disease (PD) is the second most progressive ND after Alzheimer's disease (AD), which affects the motor system and is characterized by the loss of dopaminergic neurons from the nigrostriatal pathway in the midbrain, leading to bradykinesia, rigidity, resting tremor, postural instability and non-motor symptoms such as cognitive declines, psychiatric disturbances, autonomic failures, sleep difficulties, and pain syndrome. Coconut oil (CO) is an edible oil obtained from the meat of Cocos nucifera fruit that belongs to the palm family and contains 92% saturated fatty acids. CO has been shown to mediate oxidative stress, neuroinflammation, mitochondrial dysfunction, apoptosis and excitotoxicity-induced effects in PD in various in vitro and in vivo models as a multi-target bioagent. CO intake through diet has also been linked to a decreased incidence of PD in people. During digestion, CO is broken down into smaller molecules, like ketone bodies (KBs). The KBs then penetrate the blood-brain barrier (BBB) and are used as a source of energy its ability to cross BBB made this an important class of natural remedies for the treatment of ND. The current review describes the probable neuroprotective potential pathways of CO in PD, either prophylactic or therapeutic. In addition, we briefly addressed the important pathogenic pathways that might be considered to investigate the possible use of CO in neurodegeneration such as AD and PD.

Anti-inflammatory role of SGLT2 inhibitors as part of their anti-atherosclerotic activity: Data from basic science and clinical trials.

Atherosclerosis is a progressive inflammatory disease leading to mortality and morbidity in the civilized world. Atherosclerosis manifests as an accumulation of plaques in the intimal layer of the arterial wall that, by its subsequent erosion or rupture, triggers cardiovascular diseases. Diabetes mellitus is a well-known risk factor for atherosclerosis. Indeed, Type 2 diabetes mellitus patients have an increased risk of atherosclerosis and its associated-cardiovascular complications than non-diabetic patients. Sodium-glucose co-transport 2 inhibitors (SGLT2i), a novel anti-diabetic drugs, have a surprising advantage in cardiovascular effects, such as reducing cardiovascular death in a patient with or without diabetes. Numerous studies have shown that atherosclerosis is due to a significant inflammatory burden and that SGLT2i may play a role in inflammation. In fact, several experiment results have demonstrated that SGLT2i, with suppression of inflammatory mechanism, slows the progression of atherosclerosis. Therefore, SGLT2i may have a double benefit in terms of glycemic control and control of the atherosclerotic process at a myocardial and vascular level. This review elaborates on the anti-inflammatory effects of sodium-glucose co-transporter 2 inhibitors on atherosclerosis.

Hepatoprotective Plants from Bangladesh: A Biophytochemical Review and Future Prospect.

Liver diseases are quite prevalant in many densely populated countries, including Bangladesh. The liver and its hepatocytes are targeted by virus and microbes, as well as by chemical environmental toxicants, causing wide-spread disruption of metabolic fuctions of the human body, leading to death from end-stage liver diseases. The aim of this review is to systematically explore and record the potential of Bangladeshi ethnopharmacological plants to treat liver diseases with focus on their sources, constituents, and therapeutic uses, including mechanisms of actions (MoA). A literature survey was carried out using Pubmed, Google Scholar, ScienceDirect, and Scopus databases with articles reported until July, 2020. A total of 88 Bangladeshi hepatoprotective plants (BHPs) belonging to 47 families were listed in this review, including Euphorbiaceae, Cucurbitaceae, and Compositae families contained 20% of plants, while herbs were the most cited (51%) and leaves were the most consumed parts (23%) as surveyed. The effect of BHPs against different hepatotoxins was observed via upregulation of antioxidant systems and inhibition of lipid peroxidation which subsequently reduced the elevated liver biomarkers. Different active constituents, including phenolics, curcuminoids, cucurbitanes, terpenoids, fatty acids, carotenoids, and polysaccharides, have been reported from these plants. The hepatoameliorative effect of these constituents was mainly involved in the reduction of hepatic oxidative stress and inflammation through activation of Nrf2/HO-1 and inhibition of NF-κB signaling pathways. In summary, BHPs represent a valuable resource for hepatoprotective lead therapeutics which may offer new alternatives to treat liver diseases.

Amaranthus spinosus Attenuated Obesity-Induced Metabolic Disorders in High-Carbohydrate-High-Fat Diet-Fed Obese Rats.

Amaranthus spinosus is a common vegetable of Bangladesh and well-known for its ethnomedicinal uses. In this study, we have evaluated the ability of powdered supplementation, methanol extract, and aqueous extract of A. spinosus in attenuating in high-carbohydrate-high-fat (HCHF) diet-induced obesity and associated metabolic disorders in female obese rates. Several parameters have been analyzed in this study including body weight, organ weight, fat deposition, glycemic status, lipid levels, hepatic and renal biomarkers, hepatic antioxidant status, and hepatosteatosis. All three samples of A. spinosus significantly reduced weight gain, organ weight, and abdominal fat deposition. Improved glucose tolerance and lipid parameters were seen in obese rats administered with A. spinosus powder, methanol extract, and aqueous extract. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and creatine kinase levels were normalized by the test samples. A. spinosus boosted hepatic antioxidant levels including reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Histopathology of liver tissue revealed increased fat infiltration and higher steatosis score in HCHF diet-fed obese rats which was brought down by A. spinosus. Analyzing all the results it can be concluded that this medicinal herb is beneficial in the management of obesity and obesity-induced metabolic disorders, making it a prospective food supplement.

Nutrition and antioxidant profiling in the unpolished and polished grains of eleven indigenous aromatic rice cultivars.

The present study emphasized on the yet-unexplored exhaustive analyses of nutritional and antioxidant parameters in the unpolished and polished grains of eleven indigenous aromatic rice varieties. Tulaipanji appeared to be a highly demanding variety by virtue of having sufficient levels of micronutrients like Fe, Zn and Cu (linked with higher expression of fer2, ZIP and NAS3), inorganic phosphorus, hexose sugars, total amino acids and lysine (correlated with higher expression of glutelin and RLRH1), tocopherol (due to higher HGGT expression), total phenolic content, flavonoids, anthocyanins (concomitant with higher expression of PPO, PAL and ANS), LOX activity and LOX1 gene expression, and overall higher total antioxidant capacity, particularly in the polished grains. The importance of IET-21261, with regard to higher content of phytic acid and total phosphorus (with high IPK1 expression), ß-carotene (with high PSY expression) and tocopherol (with high HGGT expression), and of Kalonunia, with respect to cysteine and γ-oryzanol in the polished grains, was also significant. Lower α-amylase enzyme activity and α-amylase expression led to considerable starch accumulation, with lower sucrose content, in the unpolished grains of Radhunipagal and polished grains of Pusa Basmati-1. Paramanya registered the highest content of thiamine and TH1 expression, together with minimum methylglyoxal level (low TPI expression). Paramanya and Radhunipagal maintained a higher pool of majority of the nutritional and antioxidant components in their unpolished grains. The polished grains of all the genotypes showed strikingly lower nutritional constituents, as compared to unpolished grains. The knowledge gained from this study will largely provide a road map to the farmers and rice consumers for making proper choice of the aromatic genotypes for large-scale cultivation and dietary consumption to derive maximum nutritional benefits.

Investigation of Electrical Characteristics in a Ferroelectric L-Patterned Gate Dual Tunnel Diode TFET.

This paper presents a ferroelectric L-patter- ned gate TFET with heavily doped (p++ type) dual tunnel diodes (DTDs), which analyzes the concept of negative capacitance as well as vertical tunneling. The tunnel junction and the channel direction are perpendicular that facilitates a broad area of the tunnel junction. Furthermore, ON current is enhanced due to the introduction of n+ pocket. To exaggerate the [Formula: see text] ratio, the device architecture is designed systematically by optimizing the ferroelectric and pocket thickness. The cumulated holes are extricated by the tunnel current produced by the DTDs, reducing the kink effect. An enhanced ON current of the order of 10-5 A/ [Formula: see text] with a minimal subthreshold swing (SS) of 29 mV/decade is achieved. The characteristics of the proposed TFET structure is compared with the existing TFET designs, and the proposed design proves to be an appropriate device for high performance and ultra-low-power applications.

In Silico Drug Target Discovery Through Proteome Mining from M. tuberculosis: An Insight into Antivirulent Therapy.

AIM AND OBJECTIVE: One of the challenges to conventional therapies against Mycobacterium tuberculosis is the development of multi-drug resistant pathogenic strains. This study was undertaken to explore new therapeutic targets for the revolutionary antivirulence therapy utilizing the pathogen's essential hypothetical proteins, serving as virulence factors, which is the essential first step in novel drug designing. METHODS: Functional annotations of essential hypothetical proteins from Mycobacterium tuberculosis (H37Rv strain) were performed through domain annotation, Gene Ontology analysis, physicochemical characterization and prediction of subcellular localization. Virulence factors among the essential hypothetical proteins were predicted, among which pathogen-specific drug target candidates, non-homologous to human and gut microbiota, were identified. This was followed by druggability and spectrum analysis of the identified targets. RESULTS AND CONCLUSION: The study successfully assigned functions of 83 essential hypothetical proteins of Mycobacterium tuberculosis, among which 25 were identified as virulence factors. Out of 25, 12 virulence factors were observed as potential pathogen-specific drug target candidates. Nine potential targets had druggable properties and rest three were considered as novel targets. Exploration of these targets will provide new insights into future drug development. Characterization of subcellular localizations revealed that most of the predicted targets were cytoplasmic which could be ideal for intracellular drugs, while two drug targets were membranebound, ideal for vaccines. Spectrum analysis identified one broad-spectrum and 11 narrowspectrum targets. This study would, therefore, instigate designing novel therapeutics for antivirulence therapy, which have the potential to serve as revolutionary treatment instead of conventional antibiotic therapies to overcome the lethality of antibiotic-resistant strains.

Differential fluoride uptake induces variable physiological damage in a non-aromatic and an aromatic indica rice cultivar.

The current study illustrates the systemic damages caused by increasing concentration of fluoride in non-aromatic rice variety, IR-64 and aromatic rice Gobindobhog (GB). Analysis of the physiological parameters like shoot length, root length and electrolyte leakage along with crucial damage indices like chlorophyll, malondialdehyde, H2O2 and protease activity indicated higher fluoride adaptation in GB compared to IR-64. IR-64 exhibited unregulated fluoride bioaccumulation when exposed to 25 mg L-1 NaF stress, whereas fluoride uptake in GB was much regulated. Gene expression studies proposed that CLC2 rather than CLC1 mediated the fluoride import. Fluoride also triggered higher P-H+/ATPase accumulation in GB compared to IR-64, thus highlighting efficient homeostasis in stressed GB. Unlike IR-64, GB could maintain photosynthesis (RuBisCo expression), sugar metabolism (α-amylase expression and activity), glycolysis and Krebs cycle even under high concentration of fluoride stress. Fluoride also inhibited nitrate reductase activity in both the cultivars. The present research illustrates differential phytotoxicity emerging out of fluoride accumulation in rice seedlings, highlighting that IR-64 is a highly susceptible variety, whereas GB exhibits physiological plasticity and is better adapted to higher concentrations of fluoride.

Differential levels of metabolites and enzymes related to aroma formation in aromatic indica rice varieties: comparison with non-aromatic varieties.

Accounting for aroma production in different aromatic indica rice varieties based on variations in the levels of concerned metabolites and enzymes is poorly explored. The present investigation was, therefore, focused on unraveling the differential levels of metabolites and activities of enzymes related to aroma formation in eleven indigenous aromatic rice varieties, as compared with four non-aromatic varieties. The levels of metabolites such as proline (Pro) and Δ1-pyrroline-5-carboxylate (P5C), and the activity of related enzymes such as proline dehydrogenase (PDH), Δ1-pyrroline-5-carboxylate synthetase (P5CS), and ornithine aminotransferase (OAT) were comparatively higher in the aromatic varieties, with Kalonunia and Tulaipanji registering the highest Pro, Kalonunia the highest P5C content, Gobindobhog with the highest PDH activity, Gobindobhog and Tulaipanji with the highest P5CS, and Pusa Basmati-1 with the highest OAT activity. The levels of putrescine (Put) and γ-aminobutyric acid (GABA) were comparatively lower in aromatic varieties, with concomitant higher diamine oxidase (DAO) activity, especially in the varieties Gobindobhog and Tulaipanji. The betaine-aldehyde dehydrogenase 2 (BADH2) enzyme activity was remarkably lesser in aromatic varieties, especially Radhunipagal and Gobindobhog. Though the metabolites such as glycine-betaine and higher polyamines such as spermidine and spermine showed no specific trend with respect to their quantitative level in either aromatic or non-aromatic varieties, they were notably lower in the aromatic varieties such as Gobindobhog, Kalonunia, and Tulaipanji, indicating a possibility of their involvement in aroma formation. Therefore, the levels of metabolites such as Pro, P5C and methylglyoxal (MG), and the activity of enzymes such as PDH, P5CS, OAT, and DAO were comparatively higher in the aromatic rice varieties than the non-aromatic ones, whereas the levels of Put, GABA, and BADH2 were lower. Overall, the present study showed that there exist variations in the accumulations of such metabolites as well as differential activity of enzymes controlling their production, which altogether regulate generation of aroma in aromatic varieties.