An in silico approach for identification of lead compound as FtsZ inhibitor.

The remarkable conservation of the FtsZ among Gram-positive and Gram-negative bacteria, a crucial GTPase in bacterial cell division, has emerged as a promising antibacterial drug target to combat antibacterial resistance. There have been several coordinated efforts to develop inhibitors against FtsZ which can also serve as potential candidates for future antibiotics. In the present study, a natural product-like library (≈50,000 compounds) was employed to conduct HTVS against Staphylococcus aureus FtsZ protein (PDB Id: 6KVP). Additionally, molecular docking was carried out in two modes, SP and XP docking, using the Schrödinger suite. The glide scores of ligands obtained by XP docking were further summarized and compared with the control ligands (ZI1- co-crystal and PC190723-a compound undergoing clinical trial). Using the Prime-MM-GBSA approach, BFE calculations were performed on the top XP-scored ligands (≈598 compounds). These hits were also evaluated for ADMET parameters using the Qikprop algorithm, SwissADME, and in silico carcinogenicity testing using Carcinopred-El. Based on the results, ligand 4-FtsZ complex was considered for the 300 ns MDS analysis to get insights into its binding modes within the catalytic pocket of FtsZ protein. The analysis revealed that the amide linkage sandwiched between the triazole and 1-oxa-8-azaspirodecan-8-ium moiety (Val203) as well as the aminoethyl group present at 1st position on the triazole moiety (Leu209, Leu200, Asp210, and Ala202) were responsible for the FtsZ inhibitory activity, owing to their crucial interactions with key amino acid residues. Further, the complex also displayed good protein-ligand stability, ultimately predicting ligand 4 as a potent lead compound for the inhibition of FtsZ. Thus, our in silico findings will serve as a framework for in-depth in-vitro and in-vivo investigations encouraging the development of FtsZ inhibitors as a new generation of antibacterial agents.

Elucidating the role of chemokines in inflammaging associated atherosclerotic cardiovascular diseases.

Age-related inflammation or inflammaging is a critical deciding factor of physiological homeostasis during aging. Cardiovascular diseases (CVDs) are exquisitely associated with aging and inflammation and are one of the leading causes of high mortality in the elderly population. Inflammaging comprises dysregulation of crosstalk between the vascular and cardiac tissues that deteriorates the vasculature network leading to development of atherosclerosis and atherosclerotic-associated CVDs in elderly populations. Leukocyte differentiation, migration and recruitment holds a crucial position in both inflammaging and atherosclerotic CVDs through relaying the activity of an intricate network of inflammation-associated protein-protein interactions. Among these interactions, small immunoproteins such as chemokines play a major role in the progression of inflammaging and atherosclerosis. Chemokines are actively involved in lymphocyte migration and severe inflammatory response at the site of injury. They relay their functions via chemokine-G protein-coupled receptors-glycosaminoglycan signaling axis and is a principal part for the detection of age-related atherosclerosis and related CVDs. This review focuses on highlighting the detailed intricacies of the effects of chemokine-receptor interaction and chemokine oligomerization on lymphocyte recruitment and its evident role in clinical manifestations of atherosclerosis and related CVDs. Further, the role of chemokine mediated signaling for formulating next-generation therapeutics against atherosclerosis has also been discussed.

Transcriptome- and proteome-wide effects of a circular RNA encompassing four early exons of the spinal muscular atrophy genes.

Spinal muscular atrophy (SMA) genes, SMN1 and SMN2 (hereinafter referred to as SMN1/2), produce multiple circular RNAs (circRNAs), including C2A-2B-3-4 that encompasses early exons 2A, 2B, 3 and 4. C2A-2B-3-4 is a universally and abundantly expressed circRNA of SMN1/2. Here we report the transcriptome- and proteome-wide effects of overexpression of C2A-2B-3-4 in inducible HEK293 cells. Our RNA-Seq analysis revealed altered expression of ~ 15% genes (4172 genes) by C2A-2B-3-4. About half of the affected genes by C2A-2B-3-4 remained unaffected by L2A-2B-3-4, a linear transcript encompassing exons 2A, 2B, 3 and 4 of SMN1/2. These findings underscore the unique role of the structural context of C2A-2B-3-4 in gene regulation. A surprisingly high number of upregulated genes by C2A-2B-3-4 were located on chromosomes 4 and 7, whereas many of the downregulated genes were located on chromosomes 10 and X. Supporting a cross-regulation of SMN1/2 transcripts, C2A-2B-3-4 and L2A-2B-3-4 upregulated and downregulated SMN1/2 mRNAs, respectively. Proteome analysis revealed 61 upregulated and 57 downregulated proteins by C2A-2B-3-4 with very limited overlap with those affected by L2A-2B-3-4. Independent validations confirmed the effect of C2A-2B-3-4 on expression of genes associated with chromatin remodeling, transcription, spliceosome function, ribosome biogenesis, lipid metabolism, cytoskeletal formation, cell proliferation and neuromuscular junction formation. Our findings reveal a broad role of C2A-2B-3-4, and expands our understanding of functions of SMN1/2 genes.

Biogenic synthesis of CuO/ZnO nanocomposite from Bauhinia variegate flower extract for highly sensitive electrochemical detection of vitamin B2.

In this study, we report the preparation of bio-inspired binary CuO/ZnO nanocomposite (bb-CuO/ZnO nanocomposite) via the biological route using Bauhinia variegata flower extract following hydrothermal treatment. The prepared bb-CuO/ZnO nanocomposite was electrophoretically deposited (EPD) on indium tin oxide (ITO) substrate to develop bb-CuO/ZnO/ITO biosensing electrode which is employed for the determination of vitamin B2 (Riboflavin) through electrochemical techniques. Physicochemical assets of the prepared bb-CuO/ZnO nanocomposite have been extensively evaluated and make use of different characterization techniques including powder XRD, FT-IR, AFM, SEM, TEM, EDX, XPS, Raman, and TGA. Electrochemical characteristics of the bb-CuO/ZnO/ITO biosensing electrode have been studied towards vitamin B2 determination. Furthermore, different biosensing parameters such as response time, reusability, stability, interference, and real sample analysis were also estimated. From the linear plot of scan rate, charge transfer rate constant (Ks), surface concentration of electrode (γ), and diffusion coefficient (D) have been calculated, and these are found to be 6.56 × 10-1 s-1, 1.21 × 10-7 mol cm-2, and 6.99 × 10-3 cm2 s-1, respectively. This biosensor exhibits the linear range of vitamin B2 detection from 1 to 40 µM, including sensitivity and limit of detection (LOD) of 1.37 × 10-3 mA/µM cm2 and 0.254 µM, respectively. For higher concentration range detection linearity is 50-100 µM, with sensitivity and the LOD of 1.26 × 10-3 mA/µM cm2 and 0.145 µM, respectively. The results indicate that the bio-inspired nanomaterials are promising sustainable biosensing platforms for various food and health-based biosensing devices.

Identification, validation and quantification of thymoquinone in conjunction with assessment of bioactive possessions and GC-MS profiling of pharmaceutically valuable crop Nigella (Nigella sativa L.) varieties.

Background: Plants have been pivotal in traditional and modern medicine globally, with historical evidence supporting their therapeutic applications. Nigella (Nigella sativa L.) is an annual herbaceous plant of the Ranunculaceae family and is cultivated in the Middle East, Eastern Europe, and Western and Central Asia. The medicinal use of plants dates back thousands of years, documented in ancient writings from various civilizations. Alkaloids, phenolics, saponins, flavonoids, terpenoids, anthraquinones, and tannins found in plants exhibit antioxidant, immunomodulatory, anti-inflammatory, anticancer, antibacterial, and antidiabetic activities. Methodology: This study specifically examines the pharmacological potential of Nigella sativa L., emphasizing thymoquinone-a compound with diverse nutraceutical benefits. The extraction, characterization, and quantification of thymoquinone, alongside other physicochemical parameters, were carried out using ethanol through Soxhlet extraction procedures on five nigella varieties. HPLC analysis was performed to determine the maximum accumulation of thymoquinone in the released variety of the plant and the chemical composition of the seed oil isolated from Nigella sativa L., varieties utilized in the study was determined through GC-MS analysis. Results: The research revealed that the Ajmer nigella-20 variety stands out, exhibiting elevated levels of thymoquinone (0.20 ± 0.07%), antioxidants (76.18 ± 1.78%), and substantial quantities of total phenols (31.85 ± 0.97 mg GAEg-1 seed) and flavonoids (8.150 ± 0.360 mg QE 100 g-1 seed) compared to other varieties. The GC-MS profiling showed the presence of 11 major compounds in the studied varieties, with p-cymene, longifolene, and myristic acid identified as the major chemical compounds present in the oil. Conclusion: The observed variations among Nigella varieties indicate the Ajmer nigella-20 variety as particularly promising for thymoquinone and bioactive compound extraction. This study underscores Nigella's potential as a source of pharmacologically active compounds, highlighting the need for further exploration in therapeutic applications.

Transcriptome- and proteome-wide effects of a circular RNA encompassing four early exons of the spinal muscular atrophy genes.

Spinal muscular atrophy (SMA) genes, SMN1 and SMN2, produce multiple circular RNAs (circRNAs), including C2A-2B-3-4 that encompasses early exons 2A, 2B, 3 and 4. Here we report the transcriptome- and proteome-wide effects of overexpression of C2A-2B-3-4 in inducible HEK293 cells. Our RNA-Seq analysis revealed altered expression of ~ 15% genes (4,172 genes) by C2A-2B-3-4. About half of the affected genes by C2A-2B-3-4 remained unaffected by L2A-2B-3-4, a linear transcript encompassing exons 2A, 2B, 3 and 4 of SMN1/SMN2. These fifindings underscore the unique role of the structural context of C2A-2B-3-4 in gene regulation. A surprisingly high number of upregulated genes by C2A-2B-3-4 were located on chromosomes 4 and 7, whereas many of the downregulated genes were located on chromosomes 10 and X. Supporting a cross-regulation of SMN1/SMN2 transcripts, C2A-2B-3-4 and L2A-2B-3-4 upregulated and downregulated SMN1/SMN2 mRNAs, respectively. Proteome analysis revealed 61 upregulated and 57 downregulated proteins by C2A-2B-3-4 with very limited overlap with those affected by L2A-2B-3-4. Independent validations confirmed the effect of C2A-2B-3-4 on expression of genes associated with chromatin remodeling, transcription, spliceosome function, ribosome biogenesis, lipid metabolism, cytoskeletal formation, cell proliferation and neuromuscular junction formation. Our findings reveal a broad role of C2A-2B-3-4, a universally expressed circRNA produced by SMN1/SMN2.

Chemoprofiling and medicinal potential of underutilized leaves of Cyperus scariosus.

Agro-waste is the outcome of the under-utilization of bioresources and a lack of knowledge to re-use this waste in proper ways or a circular economy approach. In the Indian medicinal system, the root of Cyperus scariosus (CS) is used at a large scale due to their vital medicinal properties. Unfortunately, the aerial part of CS is treated as agro-waste and is an under-utilized bioresource. Due to a lack of knowledge, CS is treated as a weed. This present study is the first ever attempt to explore CS leaves as medicinally and a nutrient rich source. To determine the food and nutritional values of the neglected part of Cyperus scariosus R.Br. (CS), i.e. CS leaves, phytochemicals and metal ions of CS were quantified by newly developed HPLC and ICPOES-based methods. The content of the phytochemicals observed in HPLC analysis for caffeic acid, catechin, epicatechin, trans-p-coumaric acid, and trans-ferulic acid was 10.51, 276.15, 279.09, 70.53, and 36.83 µg/g, respectively. In GC-MS/MS analysis, fatty acids including linolenic acid, phytol, palmitic acid, etc. were identified. In ICPOES analysis, the significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The TPC and TFC of the CS leaves was 17.933 mg GAE eq./g and 130.767 mg QCE eq./g along with an IC50 value of 2.78 mg/mL in the DPPH assay and better antacid activity was measured than the standard (CaCO3). The methanolic extract of CS leaves showed anti-microbial activity against Staphylococcus aureus (15 ± 2 mm), Pseudomonas aeruginosa (12 ± 2 mm) and Escherichia coli (10 ± 2 mm). In silico studies confirmed the in vitro results obtained from the antioxidant, antiacid, and anti-microbial studies. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the CS leaves. This study, thus, demonstrated the medicinal significance of the under-utilized part of CS and the conversion of agro-waste into mankind activity as a pharmaceutical potent material. Consequently, the present study highlighted that CS leaves have medicinal importance with good nutritional utility and have a large potential in the pharmaceutical industry along with improving bio-valorization and the environment.

Unravelling the role of long non-coding RNAs in modulating the Hedgehog pathway in cancer.

Cancer is a multifactorial pathological condition characterized by uncontrolled cellular proliferation, genomic instability, and evasion of regulatory mechanisms. It arises from the accumulation of genetic mutations confer selective growth advantages, leading to malignant transformation and tumor formation. The intricate interplay between LncRNAs and the Hedgehog pathway has emerged as a captivating frontier in cancer research. The Hedgehog pathway, known for its fundamental roles in embryonic development and tissue homeostasis, is frequently dysregulated in various cancers, contributing to aberrant cellular proliferation, survival, and differentiation. The Hh pathway is crucial in organizing growth and maturation processes in multicellular organisms. It plays a pivotal role in the initiation of tumors as well as in conferring resistance to conventional therapeutic approaches. The crosstalk among the Hh pathway and lncRNAs affects the expression of Hh signaling components through various transcriptional and post-transcriptional processes. Numerous pathogenic processes, including both non-malignant and malignant illnesses, have been identified to be induced by this interaction. The dysregulation of lncRNAs has been associated with the activation or inhibition of the Hh pathway, making it a potential therapeutic target against tumorigenesis. Insights into the functional significance of LncRNAs in Hedgehog pathway modulation provide promising avenues for diagnostic and therapeutic interventions. The dysregulation of LncRNAs in various cancer types underscores their potential as biomarkers for early detection and prognostication. Additionally, targeting LncRNAs associated with the Hedgehog pathway presents an innovative strategy for developing precision therapeutics to restore pathway homeostasis and impede cancer progression. This review aims to elucidate the complex regulatory network orchestrated by LncRNAs, unravelling their pivotal roles in modulating the Hedgehog pathway and influencing cancer progression.

Synergistic Effect of an Antisense Oligonucleotide and Small Molecule on Splicing Correction of the Spinal Muscular Atrophy Gene.

Spinal muscular atrophy (SMA) is treated by increasing the level of Survival Motor Neuron (SMN) protein through correction of SMN2 exon 7 skipping or exogenous expression of SMN through gene therapy. Currently available therapies have multiple shortcomings, including poor body-wide distribution, invasive delivery, and potential negative consequences due to high doses needed for clinical efficacy. Here we test the effects of a combination treatment of a splice-correcting antisense oligonucleotide (ASO) Anti-N1 with the small compounds risdiplam and branaplam. We show that a low-dose treatment of Anti-N1 with either compound produces a synergistic effect on the inclusion of SMN2 exon 7 in SMA patient fibroblasts. Using RNA-Seq, we characterize the transcriptomes of cells treated with each compound as well as in combination. Although high doses of each individual treatment trigger widespread perturbations of the transcriptome, combination treatment of Anti-N1 with risdiplam and branaplam results in minimal disruption of gene expression. For individual genes targeted by the 3 compounds, we observe little to no additive effects of combination treatment. Overall, we conclude that the combination treatment of a splice-correcting ASO with small compounds represents a promising strategy for achieving a high level of SMN expression while minimizing the risk of off-target effects.

MicroRNA-21's role in PTEN suppression and PI3K/AKT activation: Implications for cancer biology.

MicroRNA-21 (miR-21) was recognized as a key figure in the intricate web of tumor biology, with a prominent role in regulating the PTEN tumor suppressor gene and the PI3K/AKT cascade. This review elucidates the multifaceted interactions between miR-21, PTEN, and the PI3K/AKT signaling, shedding light on their profound implications in cancer initiation, progression, and therapeutic strategies. The core of this review delves into the mechanical intricacies of miR-21-mediated PTEN suppression and its consequent impact on PI3K/AKT pathway activation. It explores how miR-21, as an oncogenic miRNA, targets PTEN directly or indirectly, resulting in uncontrolled activation of PI3K/AKT, fostering cancerous cell survival, proliferation, and evasion of apoptosis. Furthermore, the abstract emphasizes the clinical relevance of these molecular interactions, discussing their implications in various cancer types, prognostic significance, and potential as therapeutic targets. The review provides insights into ongoing research efforts to develop miR-21 inhibitors and strategies to restore PTEN function, offering new avenues for cancer treatment. This article illuminates the critical function of miR-21 in PTEN suppression and PI3K/AKT activation, offering profound insights into its implications for cancer biology and the potential for targeted interventions.

A super minigene with a short promoter and truncated introns recapitulates essential features of transcription and splicing regulation of the SMN1 and SMN2 genes.

Here we report a Survival Motor Neuron 2 (SMN2) super minigene, SMN2Sup, encompassing its own promoter, all exons, their flanking intronic sequences and the entire 3'-untranslated region. We confirm that the pre-mRNA generated from SMN2Sup undergoes splicing to produce a translation-competent mRNA. We demonstrate that mRNA generated from SMN2Sup produces more SMN than an identical mRNA generated from a cDNA clone. We uncover that overexpression of SMN triggers skipping of exon 3 of SMN1/SMN2. We define the minimal promoter and regulatory elements associated with the initiation and elongation of transcription of SMN2. The shortened introns within SMN2Sup preserved the ability of camptothecin, a transcription elongation inhibitor, to induce skipping of exons 3 and 7 of SMN2. We show that intron 1-retained transcripts undergo nonsense-mediated decay. We demonstrate that splicing factor SRSF3 and DNA/RNA helicase DHX9 regulate splicing of multiple exons in the context of both SMN2Sup and endogenous SMN1/SMN2. Prevention of SMN2 exon 7 skipping has implications for the treatment of spinal muscular atrophy (SMA). We validate the utility of the super minigene in monitoring SMN levels upon splicing correction. Finally, we demonstrate how the super minigene could be employed to capture the cell type-specific effects of a pathogenic SMN1 mutation.

Emerging roles of SnoRNAs in the pathogenesis and treatment of autoimmune disorders.

SnoRNAs (small non-coding RNAs) have recently gained prominence in autoimmune diseases, revealing their crucial role in modulating the immune response and contributing to disease pathogenesis. Initially known for their involvement in ribosomal RNA processing and modification, molecular biology and genomics advancements have uncovered their broader impact on cellular function, especially in autoimmune disorders. Autoimmune diseases represent conditions characterized by the immune system's erroneous attacks on self-tissues, encompassing disorders like systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. The complex etiology of these conditions involves a delicate interplay of genetic and environmental factors. Emerging evidence suggests that snoRNAs initially recognized for their housekeeping roles, extend their influence on immune regulation through diverse mechanisms. SnoRNAs have been implicated in epigenetic modification, directly affecting the gene expression profiles of immune cells. Their ability to guide site-specific changes on ribosomal RNAs and other non-coding RNAs can significantly influence the translation of proteins involved in immune response pathways. Moreover, snoRNAs interact with key immune-related proteins, modulating their functions and subsequently impacting immune cell development, activation, and tolerance. Dysregulation of snoRNA expression has been observed in various autoimmune diseases, underscoring their potential as biomarkers for disease diagnosis, prognosis, and therapeutic targets. Manipulating snoRNA expression or activity is a promising therapeutic intervention avenue, offering the potential for personalized treatment strategies in autoimmune diseases. However, there remains a need for comprehensive research efforts to elucidate the precise molecular mechanisms underlying snoRNA-mediated immune modulation. Further investigations in this domain are essential to unravel the potential of snoRNAs in autoimmune disorders.

Establishment of the mechanism of purification and levigation of green chemistry-assisted biocomposites of red ochre (Gairika): synthesis, characterization, and antibacterial, prebiotic, antioxidant, and antacid activities of the traditional Ayurvedic medicine Laghu Sutashekhara Rasa.

Gairika (red ochre) has a long history of influencing human civilization. Gairika is a rich source of nutrients used for reproductive and brain health. Gairika is mentioned as an antacid drug in Indian Ayurvedic medicine under Laghu Sutashekhara Rasa (LSR). However, a detailed study on LSR has not been reported to date. In the present study, LSR was prepared, and a pharmaceutical SOP (standardization procedure) was reported to obtain batch-to-batch reproducibility. LSR was characterized using FTIR, XRD, SEM-EDX, and TGA analyses. LSR was tested in vitro for its antacid activity. Advanced instrumentation revealed that LSR formation produced symmetrical particles (5-8 µm) with kaolin, kaolinite, quartz, goethite, and hematite, along with the phytoconstituents of Goghrita (clarified cow's butter), Shunthi, and Nagawalli, as confirmed by GC-MS/MS analysis. The FTIR study revealed the formation of a chelating complex of goethite and hematite along with their phytoconstituents. XRD analysis confirmed the presence of kaolin, kaolinite, quartz, goethite, and hematite. Using in vitro antacid experiments, LSR and Shunthi demonstrated significant antacid activity as compared to antacid drugs and standards in the market, such as CaCO3. The DPPH assay revealed IC50 values of 12.16 ± 1.23 mg/mL, which is 0.0029 of Trolox-equivalent antioxidant activity. The inhibition (18 ± 4 mm) against pathogens (S. aureus, E. coli, P. aeruginosa, and B. subtilis) and the prominent growth of gut microbiota-supported strains (S. boulardii, L. paracasei, and L. plantarum) observed on LSR formulation were indicative of LSR application as a prebiotic. Here, the mechanism of purification and levigation mentioned in the classical literature of LSR was established. Overall, purification of Gairika with cow ghee and levigation with Nagawalli may enhance the solubility, bioavailability, and shelf-life of LSR through hydration and co-crystallization mechanisms. This is the first comprehensive report on the pharmaceutical validation of LSR and its characterization. The results of the present study could contribute to the development and reliable reproduction of LSR and the utility of environmental red ochre as a medicine in combination with Shunthi (Zingiber officinale Roxb.), as prescribed under Indian Ayurvedic medicine.

Transformation of PMMA from sunlight-blocking to sunlight-activated coupled with DNH photocatalytic platform for oxidative coupling of amines and generation/regeneration of LDC/NADH.

The photocatalytic oxidation and generation/regeneration of amines to imines and leucodopaminechrome (LDC)/NADH are subjects of intense interest in contemporary research. Imines serve as crucial intermediates for the synthesis of solar fuels, fine chemicals, agricultural chemicals, and pharmaceuticals. While significant progress has been made in developing efficient processes for the oxidation and generation/regeneration of secondary amines, the oxidation of primary amines has received comparatively less attention until recently. This discrepancy can be attributed to the high reactivity of imines generated from primary amines, which are prone to dehydrogenation into nitriles. In this study, we present the synthesis and characterization of a novel polymer-based photocatalyst, denoted as PMMA-DNH, designed for solar light-harvesting applications. PMMA-DNH incorporates the light-harvesting molecule dinitrophenyl hydrazine (DNH) at varying concentrations (5%, 10%, 20%, 30%, and 40%). Leveraging its high molar extinction coefficient and slow charge recombination, the 30% DNH-incorporated PMMA photocatalyst proves to be particularly efficient. This photocatalytic system demonstrates exceptional yields (96.5%) in imine production and high generation/regeneration rates for LDC/NADH (65.27%/78.77%). The research presented herein emphasizes the development and application of a newly engineered polymer-based photocatalyst, which holds significant promise for direct solar-assisted chemical synthesis in diverse commercial applications.

Current Perspective and Mechanistic Insights on Bioactive Plant Secondary Metabolites for the Prevention and Treatment of Cardiovascular Diseases.

Cardiovascular diseases (CVDs) are one of the most prevalent medical conditions of modern era and are one of the primary causes of adult mortality in both developing and developed countries. Conventional medications such as use of aspirin, beta-blockers, statins and angiotensin- converting enzyme inhibitors involve use of drugs with many antagonistic effects. Hence, alternative therapies which are safe, effective, and relatively cheap are increasingly being investigated for the treatment and prevention of CVDs. The secondary metabolites of medicinal plants contain several bioactive compounds which have emerged as alternatives to toxic modern medicines. The detrimental effects of CVDs can be mitigated via the use of various bioactive phytochemicals such as catechin, isoflavones, quercetin etc. present in medicinal plants. Current review intends to accumulate previously published data over the years using online databases concerning herbal plant based secondary metabolites that can help in inhibition and treatment of CVDs. An in-depth review of various phytochemical constituents with therapeutic actions such as antioxidant, anti-inflammatory, vasorelaxant, anti-hypertensive and cardioprotective properties has been delineated. An attempt has been made to provide a probable mechanistic overview for the pertinent phytoconstituent which will help in achieving a better prognosis and effective treatment for CVDs.

A study on H-score threshold for p16ink4a immunoperoxidase expression in squamous cell tumours of oral cavity.

Background: Validity of various detection methods used are likely contributing factor to this wide variation of prevalence of HPV (0-73%) by using GP5/GP6/MY09/MY11 (L1) primer. PCR is a sensitive method but does not identify transcriptionally active High-risk Human papillomavirus and also does not indicate whether the virus is isolated from malignant tumour cells and non-neoplastic cells. P16ink4a Immunohistochemistry is a highly sensitive and Cost-effective surrogate marker for transcriptionally active high-risk HPV for oral cancer. Objective The aim of the present study was to evaluate the H-SCORE of p16 expression in the surface epithelial tumour sites of a large cohort of squamous cell carcinoma (SCC), severe dysplasia (SD). we sought to determine whether the p16 algorithm is reliable in Oral cavity SCC and severe dysplasia (SD). Materials and Methods: This study used Immunohistochemistry in archival Formalin-fixed paraffin embedded specimens for assessment of p16 protein expression, cytoplasmic and nuclear staining intensity was categorized based on score (range, 0-3) and presence of tumour cell staining (0-100%). Results: The majority of positive cases had low H-score of p16 staining except 3/161 (1.8%) cases of tongue SCC had positive for p16 with diffuse moderate staining with ≥2 scores. There were no significant differences in the distribution of demographic, exposure and histopathological characteristics between patients with and without P16 expression. Conclusion: The present study demonstrated that p16 expression is a reliable HPV marker in the lateral border of the tongue with tonsil involvement but no other sites of the oral cavity. Further p16 IHC detection is required in large cohort of all sites of tongue squamous cell carcinoma studies to validate the marker of HPV.

A Comparative Analysis of Phytochemicals, Metal Ions, Volatile Metabolites in Heart Wood, Stem Bark and Leaves of Salix alba L. along with in Vitro Antioxidant, Antacid, Antimicrobial Activities for Sake of Environment Conservation by Substitution of Stem Bark With Leaf.

The genus of Salix is used in food, medicine and nutraceuticals, and standardized by using the single marker compound Salicin only. Stem bark is the official part used for the preparation of various drugs, nutraceuticals and food products, which may lead to overexploitation and damage of tree. There is need to search substitution of the stem bark with leaf of Salix alba L. (SA), which is yet not reported. Comparative phytochemicals viz. Salicin, Procyanidin B1 and Catechin were quantified in the various parts of SA viz. heart wood (SA-HW), stem bark (SA-SB) and leaves (SA-L) of Salix alba L.by using newly developed HPLC method. It was observed that SA-HW and SA-L contained far better amount of Salicin, Procyanidin B and Catechin as compared to SA-SB (SA-HW~SA-L≫SA-SB). Essential and toxic metal ions of all three parts were analysed using newly developed ICP-OES method, where SA-L were founded as a rich source of micronutrients and essential metal ions as compared to SA-SB and SA-HW. GC-MS analysis has shown the presence of fatty acids and volatile compounds. The observed TPC and TFC values for all three parts were ranged from 2.69 to 32.30 mg GAE/g of wt. and 37.57 to 220.76 mg QCE/g of wt. respectively. In DPPH assay the IC50 values of SA-SB, SA-HW, and SA-L were 1.09 (±0.02), 5.42 (±0.08), and 8.82 (±0.10) mg/mL, respectively. The order of antibacterial activities against E. coli, S. aureus, P. aeruginosa, and B. subtilis strains was SA-L>SA-HW>SA-SB with strong antibacterial activities against S. aureus, and B. subtilis strains. The antacid activities order was SA-L>SA-SB>SA-HW. The leaves of SA have shown significant source of nutrients, phytochemicals and medicinal properties than SA-HW and SA-SB. The leaves of SA may be considered as substitute of stem bark to save the environment or to avoid over exploitation, but after the complete pharmacological and toxicological studies.

Intensified seed spices-based cropping systems for higher productivity, resource-use efficiency, soil fertility and profitability in arid and semi-arid regions of India.

Coriander, fenugreek, nigella etc. are collectively known as seed spices. They are "High value and low volume crops" and considered cash crops for the growers of arid and semi-arid regions of India. Coriander, fenugreek and nigella are grown during the rabi season and take hardly 130-140 days to attain full maturity. In this context, farmers are not able to develop income from available arable land round the year, even though they have sufficient resources as well as manpower. Therefore, coriander, fenugreek and nigella-based cropping systems, four of each (total 12) were evaluated during 3 consecutive years (2019-20 to 2021-22) for their productivity, resource-use efficiency, economics and soil fertility. The results showed that among the seed spices-based cropping systems, maximum system productivity (5193 kg ha-1), production efficiency (18.81 kg ha-1 day-1), water-use efficiency (2.31 kg ha-1 mm-1), economic efficiency (11.85 US $ ha-1 day-1), net return (3270 US $ ha-1), benefit:cost ratio (3.27) and available N (165.6 kg ha-1) were observed under nigella-green coriander-mungbean cropping system. Hence, seed spices growers are recommended to adopt nigella-green coriander-mungbean cropping system in order to realize better productivity, resource-use efficiency, soil fertility and profitability.

Biochemical characterization of bifunctional enzymatic activity of a recombinant protein (Bp0469) from Blautia producta ATCC 27340 and its role in the utilization of arabinogalactan oligosaccharides.

Human consumption of larch arabinogalactan has a significant effect on enhancing probiotic microflora in the gut, and it also promotes the production of short-chain fatty acids. Bacterial members of Lachnospiraceae family are important and play significant roles in maintaining our gut health. However, it is less known about biochemistry of members of this family by which they utilize non-cellulosic fiber in the gut. For enhancing this understanding, we studied that B. producta ATCC 27340 grew on arabinogalactan oligosaccharides (AGOs) as compared to polysaccharide form of arabinogalactan. Recombinant protein (Bp0469) was heterologously expressed in Escherichia coli BL21 (DE3) and revealed the optimum pH and temperature at 7.4 in phosphate buffer and 45 °C, respectively. Catalytic efficiency of recombinant Bp0469 for p-nitrophenyl (pNP)-α-L-arabinofuranoside was about half of pNP-ß-D-galactopyranoside. It also cleaved natural substrates (lactose, arabinobiose and 3-O-(ß-d-galactopyranosyl)-d-galactopyranose) and characterized AGOs in this study. Based on genomic, structural models, and biochemical characteristics, identified Bp0469 is a peculiar enzyme with two distinct domains that cleave α1-5 linked arabinobiose and ß-D-Galp-1-3/4 linkages. Overall, the study enhances the knowledge on nutritional perspective of B. producta ATCC 27340 for thriving on non-cellulosic biomass, and identified enzyme can also be used for producing industrial important AGOs.

3D incoherent imaging using an ensemble of sparse self-rotating beams.

Interferenceless coded aperture correlation holography (I-COACH) is one of the simplest incoherent holography techniques. In I-COACH, the light from an object is modulated by a coded mask, and the resulting intensity distribution is recorded. The 3D image of the object is reconstructed by processing the object intensity distribution with the pre-recorded 3D point spread intensity distributions. The first version of I-COACH was implemented using a scattering phase mask, which makes its implementation challenging in light-sensitive experiments. The I-COACH technique gradually evolved with the advancement in the engineering of coded phase masks that retain randomness but improve the concentration of light in smaller areas in the image sensor. In this direction, I-COACH was demonstrated using weakly scattered intensity patterns, dot patterns and recently using accelerating Airy patterns, and the case with accelerating Airy patterns exhibited the highest SNR. In this study, we propose and demonstrate I-COACH with an ensemble of self-rotating beams. Unlike accelerating Airy beams, self-rotating beams exhibit a better energy concentration. In the case of self-rotating beams, the uniqueness of the intensity distributions with depth is attributed to the rotation of the intensity pattern as opposed to the shifts of the Airy patterns, making the intensity distribution stable along depths. A significant improvement in SNR was observed in optical experiments.