Elucidation of escitalopram oxalate and related antidepressants as putative inhibitors of PTP4A3/PRL-3 protein in hepatocellular carcinoma: A multi-computational investigation.

Hepatocellular carcinoma (HCC) persists to be one of the most devastating and deadliest malignancies globally. Recent research into the molecular signaling networks entailed in many malignancies has given some prominent insights that can be leveraged to create molecular therapeutics for combating HCC. Therefore, in the current communication, an in-silico drug repurposing approach has been employed to target the function of PTP4A3/PRL-3 protein in HCC using antidepressants: Fluoxetine hydrochloride, Citalopram, Amitriptyline, Imipramine, and Escitalopram oxalate as the desired ligands. The density function theory (DFT) and chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters for the chosen ligands were evaluated to comprehend the pharmacokinetics, drug-likeness properties, and bioreactivity of the ligands. The precise interaction mechanism was explored using computational methods such as molecular docking and molecular dynamics (MD) simulation studies to assess the inhibitory effect and the stability of the interactions against the protein of interest. Escitalopram oxalate exhibited a comparatively significant docking score (-7.4 kcal/mol) compared to the control JMS-053 (-6.8 kcal/mol) against the PRL-3 protein. The 2D interaction plots exhibited an array of hydrophobic and hydrogen bond interactions. The findings of the ADMET forecast confirmed that it adheres to Lipinski's rule of five with no violations, and DFT analysis revealed a HOMO-LUMO energy gap of -0.26778 ev, demonstrating better reactivity than the control molecule. The docked complexes were subjected to MD studies (100 ns) showing stable interactions. Considering all the findings, it can be concluded that Escitalopram oxalate and related therapeutics can act as potential pharmacological candidates for targeting the activity of PTP4A3/PRL-3 in HCC.

Comparative study on thermo-mechanical, structural and functional properties of pectin extracted from immature wasted apples and commercial pectin.

Pectin yield of 22.22 ± 0.98 % (dry basis) was achieved from prematurely dropped Golden Delicious apples, having a light orange hue (hue value: 78.08 ± 0.04) and an overall color difference (ΔE) of 9.92 ± 0.01 compared to commercial pectin (CP). Extracted AP exhibited a lower equivalent weight (725.24 ± 29.73) and higher methoxy content (8.36 ± 0.28 %) in contrast to CP. However, a similar degree of esterification of 71.57 ± 0.79 and 70.55 ± 0.59 %, was observed in AP and CP respectively. Apple pectin demonstrated slight lower galacturonic acid (GalA) content of 68.10 ± 3.94 % in comparison to 72.31 ± 4.62 % of CP, which was further corroborated by reduced intensity in FTIR fingerprint region (912-1025 cm-1). Morphology revealed a sheet-like cloudy appearance indicating a significant presence of associated sugars whereas X-ray diffraction highlighted the highly amorphous nature of AP. AP and CP solutions (3-9 %) displayed a shear-thinning flow and viscoelastic behavior where the loss (G') moduli dominated over the storage moduli (G"). Owing to high degree of esterification, galacturonic acid content (>65 %) that aligns with commercial standards and viscoelastic behavior, the extracted AP holds promise for potential utilization in commercial applications. This study underscores the potential for sustainable utilization of prematurely dropped apples through pectin extraction, contributing to valorization of the wasted bioresource.

India's biogeochemical capacity to attain food security and remediate climate.

In order to supply wholesome food and slow down climate change, this paper covers India's agrogeological resources. The soils are the result of the weathering of rocks with ages ranging from more than a billion years to the most recent Holocene. Because they are severely deficient in vital minerals, many soils have low agricultural production. In addition to helping to fertilise soils, reduce atmospheric carbon dioxide levels, and stop the acidification of the Indian Ocean, rock powder weathering and biochar have significant positive effects on the productivity of Indian soils. The nutrient density of food is also increased which improves health and lowers the demand for and cost of medical treatment. Remineralization may help to solve Indian soil issues including soil infertility and texture. To improve soil and plant nutrition, dusts of carbonate, basic, and ultrabasic rocks are readily available at mining sites in India combined with biochar. Adding different grain sizes to the soil helps improve the texture of the soil. Silicate and carbonate rock powders enhance soil structure by promoting the creation of soil organic matter and fostering the growth of advantageous microbial communities. These processes offer a low-cost method of remineralizing soils with important macro- and micronutrients. For each significant soil/crop/climate system, an optimised application of India's rock powder resources must be determined through a national research and development programme. India's capacity to adapt to the mounting challenges of population expansion and climate change would be significantly improved by the findings of this study programme.

Elucidation of 7,8-dihydroxy flavone in complexing with the oxidative stress-inducing enzymes, its impact on radical quenching and DNA damage: an in silico and in vitro approach.

Oxidative stress (OS) has been attributed to the progression of various disorders, including cancer, diabetes, and cardiovascular diseases. Several antioxidant compounds and free radical quenchers have been shown to mitigate oxidative stress. However, large-scale randomized controlled trials of such compounds on chronic disease aversion have yielded paradoxical and disappointing results due to the constrained cognizance of their oxidative mechanisms and therapeutic targets. The current study sought to identify the potential therapeutic targets of 7,8-Dihydroxyflavone (7,8-DHF) by analyzing its interactions with the enzymes implicated in oxidative stress and also to explore its radicle quenching potential and prophylactic impact on the H2O2-induced DNA damage. Through the in silco approach, we investigated the antioxidant potential of 7,8-DHF by evaluating its interactions with the human oxidative stress-inducing enzymes such as myeloperoxidase (MPO), NADPH oxidase (NOX), nitric oxide synthase (NOS), and xanthine oxidase (XO) and a comparative analysis of those interactions with known antioxidants (Ascorbic acid, Melatonin, Tocopherol) used as controls. The best-scoring complex was adopted for the simulation analysis in investigating protein-ligand conformational dynamics. The in vitro radicle quenching potential was evaluated by performing a spectrum of antioxidant assays, and radical quenching was observed in a dose-dependent fashion with IC50 values of < 60 µM/mL. Further, we probed its anti-hemolytic potential and prophylactic impact in avian erythrocytes subjected to H2O2-induced hemolysis and DNA damage by implementing hemolysis and comet assays. The protective effect was more pronounced at higher concentrations of the drug.Communicated by Ramaswamy H. Sarma.

The relevance of acid sphingomyelinase as a potential target for therapeutic intervention in hepatic disorders: current scenario and anticipated trends.

Acid sphingomyelinase (ASMase) serves as one of the most remarkable enzymes in sphingolipid biology. ASMase facilitates the hydrolysis of sphingomyelin, yielding ceramide and phosphorylcholine via the phospholipase C signal transduction pathway. Owing to its prominent intervention in apoptosis, ASMase, and its product ceramide is now at the bleeding edge of lipid research due to the coalesced efforts of several research institutions over the past 40 years. ASMase-catalyzed ceramide synthesis profoundly alters the physiological properties of membrane structure in response to a broad range of stimulations, orchestrating signaling cascades for endoplasmic reticulum stress, autophagy, and lysosomal membrane permeabilization, which influences the development of hepatic disorders, such as steatohepatitis, hepatic fibrosis, drug-induced liver injury, and hepatocellular carcinoma. As a result, the potential to modulate the ASMase action with appropriate pharmaceutical antagonists has sparked a lot of curiosity. This article emphasizes the fundamental mechanisms of the systems that govern ASMase aberrations in various hepatic pathologies. Furthermore, we present an insight into the potential therapeutic agents used to mitigate ASMase irregularities and the paramountcy of such inhibitors in drug repurposing.

Synthesis of Iron Nanoparticles Using Sargassum wightii Extract and Its Impact on Serum Biochemical Profile and Growth Response of Etroplus suratensis Juveniles.

The present study focuses on the green synthesis of iron nanoparticles using plant extracts as reducing, capping, and stabilizing agents. Aqueous seaweed extracts with the addition of iron solution were mixed using a magnetic stirrer which resulted in a color change indicating the formation of iron nanoparticles. The iron nanoparticles were successfully synthesized using Sargassum wightii extract. The synthesized iron nanoparticles were characterized by UV-Vis spectrophotometer, Fourier transform infrared spectroscopy (FTIR), and zeta potential techniques. The UV-Vis spectra showed a peak at 412 to 415 nm. Zeta potential revealed that the synthesized iron nanoparticles were negative and positive charges. FTIR spectroscopy analysis showed the presence of chemical bond and amide group likely to be responsible for the green synthesis of iron nanoparticles. The effect of nano-iron as a dietary iron source on the growth and serum biochemical profile of Etroplus suratensis fingerlings was evaluated. Iron nanoparticles were fed to E. suratensis fingerlings for 60 days with two levels 10 mg (T1) and 20 mg (T2) and a control group without iron nanoparticles. The highest WG% and SGR and lowest FCR were observed in the T2 group which is significantly different (p < 0.05) from other groups. The serum biochemical profile showed significantly increased activity on 20 mg/kg of nano-iron-supplemented diet. The findings of the present study concluded that supplementation of nano-iron at the 20 mg/kg level to the regular fish diet has a better impact not only on growth but also on the overall health of the fish.

MicroRNA-3692-3p is overexpressed in lung tumors but may not serve as a prognostic biomarker in lung cancer patients.

BACKGROUND: We previously reported overexpression of miR-3692-3p in the serum of non-small cell lung cancer patients. However, the expression profile and clinical utility of miR-3692-3p in the tumor tissues of lung cancer patients are not yet reported. METHODS AND RESULTS: We quantified the expression levels of miR-3692-3p in the tumors and adjacent normal lung tissues of early-stage (n = 29) and tissue biopsies of locally advanced and metastatic (n = 85) lung cancer patients using TaqMan advanced miRNA assay. We correlated miR-3692-3p expression with survival outcomes, therapeutic response, and other clinicopathological variables. We also predicted the target genes of miR-3692-3p, constructed a protein-protein interaction network, and performed functional enrichment analysis using various in silico tools. We found significant overexpression of miR-3692-3p in the tumors (Log2 fold change = 3.672; p < 0.0001) and tissue biopsies (Log2 fold change = 2.08; p = 0.0001) compared to normal lung tissues of lung cancer patients. The expression of miR-3692-3p did not correlate with overall survival (OS), progression-free survival (PFS), and response to therapy. In multivariate analysis, therapeutic response emerged as an independent prognostic biomarker of OS (HR = 3.47; p = 0.022) and PFS (HR = 19.86; p < 0.001). Our in silico analysis predicted 238 target genes of miR-3692-3p. CONCLUSIONS: Overexpression of miR-3692-3p could contribute to the development of lung cancer. However, mechanistic studies are warranted to shed further light on its role in lung carcinogenesis.

Epigenetics and mitochondrial dysfunction insights into the impact of the progression of non-alcoholic fatty liver disease.

A metabolic problem occurs when regular functions of the body are disrupted due to an undesirable imbalance. Nonalcoholic fatty liver disease (NAFLD) is considered as one of the most common in this category. NAFLD is subclassified and progresses from lipid accumulation to cirrhosis before advancing to hepatocellular cancer. In spite of being a critical concern, the standard treatment is inadequate. Metformin, silymarin, and other nonspecific medications are used in the management of NAFLD. Aside from this available medicine, maintaining a healthy lifestyle has been emphasized as a means of combating this. Epigenetics, which has been attributed to NAFLD, is another essential feature of this disease that has emerged as a result of several sorts of research. The mechanisms by which DNA methylation, noncoding RNA, and histone modification promote NAFLD have been extensively researched. Another organelle, mitochondria, which play a pivotal role in biological processes, contributes to the global threat. Individuals with NAFLD have been documented to have a multitude of alterations and malfunctioning. Mitochondria are mainly concerned with the process of energy production and regulation of the signaling pathway on which the fate of a cell relies. Modulation of mitochondria leads to elevated lipid deposition in the liver. Further, changes in oxidation states result in an impaired balance between the antioxidant system and reactive oxygen species directly linked to mitochondria. Hence mitochondria have a definite role in potentiating NAFLD. In this regard, it is essential to consider the role of epigenetics as well as mitochondrial contribution while developing a medication or therapy with the desired accuracy.

Comparative study of TNF-α and vitamin D reveals a significant role of TNF-α in NSCLC in an ethnically conserved vitamin D deficient population.

Growing evidence has implicated tumor necrosis factor-alpha (TNF-α) as an important regulator of the tumor microenvironment. Moreover, various molecular epidemiological studies have proposed vitamin D deficiency to be a mediator of cancer progression. Here we comparatively analyzed the role of TNF-α and vitamin D in non-small cell lung cancer (NSCLC) in an ethnically conserved vitamin D deficient population. Confirmed NSCLC cases (n = 190) matchedfor age, gender, dwelling, and smoking against cancer-free healthy controls ((n = 200) were genotyped for TNF-α promoter polymorphisms (rs361525 and rs1800629) by PCR-RFLP. 48 NSCLC tumor and adjacent normal tissues were quantified for TNF-α mRNA expression by RT-qPCR. 48 NSCLC cases and 60 healthy controls were analyzed for TNF-α and vitamin D serum levels by ELISA and chemiluminescence respectively. Our study indicates thatrs361525 and rs1800629 bear a significant risk towards NSCLC. Both mutant genotype and mutant allele of rs361525 elicit a likelihood of NSCLC reflected by their odds ratio (OR) of 3.16 and 1.81 respectively. In case of rs1800629, the heterogeneous genotype (GA) showed two fold higher risk for NSCLC (OR-2.07, P = 0.006), which could be attributed to the presence of the mutant allele as reflected by overall frequency of mutant A allele vs wild G allele (OR-1.92, P = 0.01). A combined effect of genotypes for rs361525 and rs1800629 revealed a 3.7 fold higher risk towards NSCLC for the presence of heterozygous genotype at both loci. Our preliminary expression results showed significant increase of TNF-α mRNA expression in tumor tissues of NSCLC as compared to adjacent normal tissues [cases- 8.56 ± 3.90vs controls-4.88 ± 2.96, P < 0.0001)] which was further affirmed by extrapolation of TNF-α expression in serum (Cases- 55.75 ± 22.50vs controls- 21.46 ± 27.75, P < 0.0001). Multivariate regression analyses revealed TNF-α mRNA expression to be significantly associated with NSCLC cases less than 50 years of age (P < 0.05). In comparison to the putative role of TNF-α in NSCLC as suggested by the results observed, vitamin D showed no significance towards any of the analyzed parameters or with the risk of NSCLC. This study suggests that TNF-α could be a potential mediator of NSCLC which bears important clinical implications and could be an important therapeutic marker in NSCLC.

Computational analysis and functional characterisation of Tor putitora toll-like receptor 4 with the elucidation of its binding sites for microbial mimicking ligands.

In the current study, full-length Toll-like receptor 4 (TLR4) cDNA was cloned and characterised in Tor putitora, an important fish inhibiting Himalayan rivers. The complete coding sequence of TpTLR4 is 2457 bp with nine key structural domains, including six leucine-rich repeats (LRRs). The phylogenetic tree revealed that TpTLR4 showed the closest relationship with TLR4 of Cyprinus carpio (96%), Labeo rohita (91%) and Megalobrama amblycephala (88%), all belonging to the Cyprinidae family. CELLO2GO tool revealed that TpTLR4 protein is highly localised in the plasma (67.7%), and the protein has a strong association with myeloid differentiation primary response 88 (MYD88) followed by Tumor necrosis factor receptor-associated factor (TRAF) family. In the toll-interleukin-1 receptor (TIR) domain of TpTLR4, the proline is replaced by the alanine amino acid, thus may give plasticity to the receptor to recognise both bacterial and viral ligands. Molecular docking has revealed that TpTLR4 showed the strongest affinity towards poly (I:C) with the binding energy of -6.1 kcal/mol and five hydrogen bonds among all ligands. Based on our molecular docking results, it can be presumed that TpTLR4 can sense bacterial, fungal and viral molecular patterns with binding sites mainly present in the TpTLR4 LRR9 motif, which spans between 515 and 602 amino acids. Tor putiora TLR4 transcript was ubiquitously expressed in all the tested fish tissues. Although, transcript level was found to be highest in blood and spleen followed by the kidney. The TpTLR4 transcripts showed peak expression in spleen and kidney at 12 h post-injection (hpi) (p < 0.05) of poly (I:C). The constitutive expression of TpTLR4 in various tissues, up-regulation in different tissues and strong binding affinities with poly (I:C) indicate that TpTLR4 may play an essential role in sensing pathogen-associated molecular patterns (PAMPs), particularly of viral origin.

Distribution, sources and toxicity of heavy metals in surface sediments of north western Karnataka, south India.

This study presents spatial distribution, sources and toxicological risks of As, Cr, Cu, Hg, Ni, Pb, and Zn in the surface sediments from north-western Karnataka, southern India. Heavy metals (except Hg) are 1-5 times enriched than upper continental crust. High concentration of Cr, Ni, Cu, and Zn is in the central Kudalgaon, Devarayi, and Tavargatti and in the south-western Ganeshgudi area, whereas Arsenic is enriched in the north-eastern Alnavar, Kakkeri,Tavargatti and Pb, and Hg in the north-western Kapoli, Devarayi, Manjarpal villages. The ecological risk index, toxic risk index, and mean probable-effects-levels quotient of heavy metals suggest that ~ 40% of the area is prone to very high risk especially for Cr and As to the hydrological, biological, and ecological systems. Multivariate statistical analysis suggests possible geogenic sources for Ni, Cr, Cu, and Zn and anthropogenic sources such as emissions from vehicles and agricultural sectors for As, Hg, and Pb. This study is the first of its kind in the area, which will help, in better formulation of environmental pollution and risk related remedial measures to conserve the natural ecosystem and the well-being of humans.

An immediate post op and follow up assessment of circulating adipo-cytokines after bariatric surgery in morbid obesity.

BACKGROUND: Bariatric surgery has emerged as a promising treatment for improving adipose tissue dysfunction in obesity, but the mechanisms for such amelioration are still not known. This study comprehensively explores a panel of adipo-cytokines in individuals with obesity undergoing bariatric surgery, in conjunction with markers of insulin resistance, at three time points i.e., pre-op, immediate post-op and 6 months post-surgery. METHODS: It is a case-control prospective study among obese individuals undergoing bariatric surgery (BMI ≥35 kg/m2, n=30) and non-obese subjects (BMI <25 kg/m2, n=30), comparing the levels of serum adiponectin, resistin, C-Reactive Protein (CRP), Interleukin (IL)-6 and 8, Monocyte chemoattractant protein (MCP)-1 and Tumor necrosis factor (TNF)-α between them. The same were followed at immediate and 6-month post-op periods in the former group. The serum markers were correlated with the markers of Insulin resistance like HOMA-IR, HOMA-ß and QUICKI. RESULTS: A significant increase in adiponectin was seen after weight loss in obese group (17.54 ± 1.31 µg/mL at baseline vs 68.76 ± 1.84 µg/mL at 6- month post-surgery). CRP being an acute phase protein showed significant higher levels at immediate post-op period but declined even below its baseline at 6 months after surgery (33.34 ± 16.85 µg/mL at baseline vs 59.85 ± 23.12 µg/mL at immediate post-op vs 9.66 ± 1.84 µg/mL at 6 months post-operatively). Few inconsistencies were observed in the trajectories of IL-6 and TNF-α, while other pro-inflammatory markers indicated resolution after surgery. CONCLUSION: Bariatric surgery alleviated the systemic inflammation, correlating with improved insulin resistance in individuals with obesity.

Evaluation of the programmed death-ligand 1 mRNA expression and immunopositivity and their correlation with survival outcomes in Indian lung cancer patients.

The presence of membranous immunopositivity of programmed death-ligand 1 (PD-L1) in tumors serves as a key determinant of response to immune checkpoint inhibitors. However, there are very limited studies on the evaluation of the PD-L1 mRNA expression and immunopositivity and their correlation with therapeutic response and survival outcomes, especially in Indian lung cancer patients. In this prospective study, conducted between 2017 and 2020, we collected biopsies and surgically resected tumors from 173 lung cancer patients. PD-L1 immunopositivity and mRNA expression were determined by immunohistochemistry using SP263 assay and qRT-PCR, respectively. PD-L1 expression was correlated with various clinicopathological variables, response to therapy, and survival outcomes using appropriate statistical methods. The median age was 60 years (range 33-81 years) with the majority of patients being male (86.5%) and smokers (83%). Histologically, the majority of patients were non-small cell lung cancer (89.4%) and of squamous cell carcinoma histology (64.3%). PD-L1 immunopositivity in tumor cells (tumor proportion score (TPS) ≥ 1%) was detected in 37.6%, while high immunopositivity (TPS ≥ 50%) was detected in 16.8% of lung cancer patients. Almost 76% of lung cancer patients with PD-L1 TPS ≥ 50% belonged to PD-L1 mRNA high-expression group. PD-L1 mRNA expression and immunopositivity did not correlate with response to therapy and survival outcomes. We conclude that PD-L1 immunopositivity and mRNA expression do not seem to serve as a prognostic biomarker for lung cancer patients treated with chemotherapy. More prospective studies should be planned to evaluate the predictive and prognostic relevance of PD-L1 expression in Indian lung cancer patients being treated with immune checkpoint inhibitors.

The prominence of potential biomarkers in the diagnosis and management of hepatocellular carcinoma: Current scenario and future anticipation.

Hepatocellular carcinoma (HCC) is one of the most aggressive and truculent types of cancer. Early detection of HCC is a massive concern that can boost the overall survival rates of HCC patients. As a result, there is a continual quest for advancements in screening, diagnosis, and treatment strategies to enhance the prognosis at its early stages. However, the confluence of inflammation and cirrhosis hampers the early detection of HCC. The analysis of different types of biomarkers such as tissue biomarkers, serum biomarkers, protein biomarkers, autoantibody markers, and improved imaging techniques has played a vital role in ameliorating HCC monitoring responses. Therefore biomarkers that can identify HCC early with a high degree of sensitivity and specificity might be prodigiously serviceable in the diagnosis and treatment of this notorious disorder. This study offers an overview of the contemporary understanding of several types of biomarkers implicated in hepatocarcinogenesis and their applications in monitoring, diagnosis, and prognosis presage. In additament, we address the role of image techniques associated with HCC diagnosis.

Targeting molecular signal transduction pathways in hepatocellular carcinoma and its implications for cancer therapy.

Hepatocellular carcinoma is a substantial health concern. It is currently the third dominating cause of mortality associated with cancer worldwide. The development of hepatocellular carcinoma is an intricate process that encompasses the impairment of genetic, epigenetic, and signal transduction mechanisms contributing to an aberrant metabolic system, enabling tumorigenesis. Throughout the past decade, research has led to the revelation of molecular pathways implicated in the progression of this notorious disorder. The altered signal transduction pathways, such as the mitogen-activated protein kinase pathway, phosphoinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway, WNT/ß-catenin pathway, hepatocyte growth factor/c-MET pathway, and just another kinase/signal transducers and activators of transcription signaling pathway is of much therapeutic significance, as targeting them may avail to revert, retard or avert hepatocarcinogenesis. The present review article sums up the contemporary knowledge of such signaling mechanisms, including their therapeutic targets and betokens that novel and efficacious therapies can be developed only by the keen understanding of their character in hepatocarcinogenesis. In additament, we address the role of consequential therapeutic agents and preclinical nondrug therapies known for combating hepatocarcinogenesis.

Serum Adipocytokines Levels and Their Association with Insulin Sensitivity in Morbidly Obese Individuals Undergoing Bariatric Surgery.

BACKGROUND: Obese adipose tissue secretes a variety of adipocytokines that act as metabolic regulators with complex mechanisms. Our objective was to compare serum concentration of a panel of adipocytokines between obese and non-obese individuals and identify any distinct patterns correlating with insulin sensitivity in obesity. METHODS: We designed a cross-sectional study among obese (body mass index [BMI] ≥30 kg/m2, n=62) and non-obese (BMI <25 kg/m2, n=32) individuals to compare circulating levels of the adipokines, such as adiponectin and resistin in conjunction with the measurement of the levels of inflammatory cytokines including C-reactive protein (CRP), interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α using Luminex multiplex immunoassay with drop array technology. Correlations between circulating adipocytokine levels and those of multiple well-established markers of insulin resistance including homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of ß-cell function (HOMA-ß) and quantitative insulin sensitivity check index were also established. RESULTS: CRP, IL-8, MCP-1, and TNF-α levels were higher in obese than non-obese individuals; the CRP and IL-8 differences were statistically significant. CRP correlated significantly with markers of insulin resistance (fasting plasma insulin, HOMA-IR, and QUICKI), and adiponectin correlated with HOMA-ß in obese individuals. We divided the group of obese individuals on the basis of HOMA-IR levels into insulin-resistant (IR; HOMA-IR ≥2.5) and insulin-sensitive (IS; HOMA-IR <2.5) groups; and 43 out of 62 participants were IR despite comparable BMIs. An overall proinflammatory profile was compared between IR and IS obese, though the values were higher in IR obese but the difference was not significant. CONCLUSION: Obesity is associated with a general inflammatory milieu and a crosstalk between adipocytokines and insulin resistance is complex as well as multifactorial.

Cloning, characterization and ontogenetic expression profile of RAG-2 and IgM in angelfish (Pterophyllum scalare).

Early larval developmental stages of fish are highly susceptible to opportunistic pathogens until the complete maturation of the lymphoid organs. Knowledge of the expression pattern of important markers of adaptive immune system during the ontogenetic development is essential before vaccinating the fish. In the present study, Pterophyllum scalare (angelfish) was taken to explore the relative expression profile of developmental markers of adaptive immunity, recombination activating gene-2 (RAG-2) and immunoglobulin M (IgM). The fishes were bred and early developmental stages (0-45 days post-hatched) were used to assess the expression profile. The genes, RAG-2 and IgM were cloned and sequenced with the base pair lengths of 1958 bp and 225 bp respectively. The mRNA expression of RAG-2 appeared at insignificant level at the first day of hatching, but the expression was significantly increased from 24 dph (days post-hatching) onwards and reached its peak at 27 dph. The results proved that the maturation of lymphoid organs was completed at 27 dph as the respective protein is involved in the V(D)J recombination, important for the maturation of lymphoid organs. A similar trend was also observed in the mRNA transcript levels of IgM gene and a significantly high expression was detected from 27 dph onwards. The present study suggested that the suitable time for vaccination in P. scalare could be taken at 27 dph, as the maturation and development of lymphoid organs is completed thus helps in stimulating the adaptive response of immunity against any pathogen.

Curcuma longa and Trigonella foenum graecum-enriched nutrient mixture from germinated Macrotyloma uniflorum and Vigna radiate ameliorate nonalcoholic fatty liver diseases in rats.

The prevalence of nonalcoholic fatty liver is increasing due to modern lifestyle. Germinated and dehulled Macrotyloma uniflorum and Vigna radiate were shown to have enhanced nutrients. Curcuma longa and Trigonella foenum graecum were proven hepatoprotective.The supplementation of the nutrient herbal mixture to the MCD diet-induced steatosis shows reduced hepatic fat accumulation and lipid profile, and liver injury markers in serum also reserved in normal. Increased serum albumin in the treatment group indicates that the liver function is enhanced than that of steatosis. The supplementation of the herbal mixture has preserved the hepatic antioxidant. Zymographic analysis of matrix metalloproteinase, western blot determination of α-SMA, and histological evolution (H&E, Sirius red) depicted reduced fibrosis and reveled management of hepatic stellate cells in quiescent form. The present study concludes that the herbal mixture has reduced hepatocyte fat accumulation in steatotic animals, and curtailed the oxidative stress, further it prevents the progression of steatohepatitis. PRACTICAL APPLICATIONS: Fatty liver diseases can be treated by modulating the diet composition such as consuming food rich in the nutrient herbal mixture. In this study, the nutrient mixture was made with dynamic food processing techniques such as germination, dehulling, and milling to augment the nutritional contents. Besides, Macrotyloma uniflorum, Vigna radiate, Curcuma longa, and Trigonella foenum graecum were used to improve the medicinal value and antioxidant. This formulation could target the various stages of NAFLD. This study revealed that the nutrient herbal mixture reduces the steatosis of the liver and curtailed the progression of steatohepatitis from hepatic steatosis. Since the edible foodstuff was used to make the nutrient mixture, it has excellent clinical application.

Nutrient mixture from germinated legumes: Enhanced medicinal value with herbs-attenuated liver cirrhosis.

Among various food processing strategies, germination and dehulling enhance the nutritional content of the food, and the addition of herbs to this could improve the medicinal value. The milled powders of germinated Macrotyloma uniflorum (horse gram) and Vigna radiata (green gram) were used to make the nutrient mixture. Further, Curcuma longa (turmeric) and Trigonella foenum graecum (fenugreek) were used to improve its medicinal value. The prepared nutrient mixture has high nutritional value, antioxidant potential, and reduced antinutrient factors. Supplementation of nutrient mixture reduced oxidative stress-mediated hepatocyte injury on the CCl4 -induced liver cirrhosis model. Further, histological examination (H&E and Sirius red), matrix metalloproteinase gelatin zymography, and Western blot revealed the management of hepatic stellate cells in an inactive stage thereby reduced cirrhosis. These findings conclude that the supplementation of nutrient mixture formulation protected and effectively prevented liver cirrhosis. PRACTICAL APPLICATIONS: This study has a good impact on nutritional therapy for liver diseases. Many of the chronic liver diseases are associated with severe malnutrition and hypoalbuminemia, which further worsens the condition. This study would emphasize the nutritional therapy to treat such imbalance and enriching the medicinal value of nutrition mixture with herbs could target different pathophysiological changes and provide better defense in liver disease patients. Since this nutrient mixture is from common edible natural resources, it could reach the pharmaceutical industry's attention to the highest production and marketing.

Expression and activity of key lipases during the larval development of walking catfish (Clarias magur).

The study was conducted to investigate the expression and activity of key lipolytic enzymes during the ontogenetic development of Clarias magur. After partial characterization, the messenger RNA (mRNA) expression analysis of lipoprotein lipase (LPL), pancreatic triacylglycerol lipase (PL), and bile salt-activated lipase (BAL) genes along with the specific lipase activity were performed in larvae from Day 1 after hatching till 34-day posthatch (dph). Heterogeneous patterns of mRNA expression were shown by the important lipolytic enzymes and were detected before first exogenous feeding during the yolk-sac stage. LPL started increasing from 13 dph and peaked at 16 dph followed by a declining trend till 34 dph. However, the PL observed to be peaking at 9, 22, and 30 dph. Similarly, BAL showed an increasing trend from 11 to 22 dph with a significantly high level of mRNA expression at 16 dph. Later, the specific lipase activity was evaluated which appears at Day 1 after hatching with a progressive increase from 7 to 16 dph and a further declining trend afterwards with a peak at 22 dph. The results indicated the development of exocrine pancreas at 16 dph. Furthermore, the transcript levels and the activity of lipases were regulated with the age. Hence, the present study can be helpful in devising different strategies containing optimum lipid levels at a suitable stage of development for improving the survival during larval rearing. Furthermore, the study could be a baseline for elucidating the optimized dietary lipid levels of this catfish during its larval rearing.