Phytochemical Screening and Antidiabetic Efficacy of Balanites aegyptiaca Seed Extract and Their Silver Nanoparticles on Muscle and Pancreatic Cell Lines.

Balanites aegyptiaca (L.) Delile, a member of the Zygophyllaceae family, is commonly known as the desert date. This tree is famous for yielding edible fruits and is esteemed for its nutritional richness and diverse health advantages. The primary aim of this research was to assess the potential antidiabetic and cytotoxic effects of seed extracts from B. aegyptiaca and its AgNPs for the first time on C2C12 and MIN6 cells, focusing on glucose uptake and insulin secretion, respectively. Additionally, the seed extracts underwent column chromatography through different solvent systems, resulting in the isolation of five distinct fractions with a mixture of methanol and water as an eluting solvent in different ratios. Comprehensive characterization of the aqueous seed extract was carried out using GC-MS and UPLC-MS. The study determined that the aqueous seed extract exhibited no toxicity at any tested concentration (6.25-100 µg/mL) on both cell types. The calculated IC50 values were 206.00 and 140.44 µg/mL for C2C12 and MIN6 cells, respectively, for seeds of AgNPs. Additionally, the aqueous seed extract and their AgNPs significantly increased glucose uptake by 150.45% and 156.00% of the control in C2C12 cells at a concentration of 100 µg/mL. Insulin secretion was also notably enhanced by 3.47- and 3.92-fold of the control after administering seed extracts and AgNPs, respectively, at 100 µg/mL. GC-MS and UPLC-MS analyses identified various compounds across different categories. Notably, the F2 fraction (methanol and water in ratio of 80:20 as eluting solvent) exhibited the highest glucose uptake activity (156.81% of control), while the F3 fraction (methanol and water in ratio of 70:30 as eluting solvent) fraction demonstrated the highest insulin secretion activity (3.70 folds of the control) among all fractions at 100 µg/mL. GC-MS analysis was employed to characterize both fractions, aiming to identify the compounds contributing to their antidiabetic potential. The study's findings concluded that both seed extracts and their AgNPs possess significant antidiabetic properties, with elevated activity observed in the case of AgNPs in both assays. Various compounds, including diosgenin, oleic acid, linoleic acid and palmitic acid esters were detected in the seed extracts, known for their reported antidiabetic and hypoglycemic effects.

Proteomic profiling of Arabidopsis G-protein ß subunit AGB1 mutant under salt stress.

Salt stress is a limiting environmental factor that inhibits plant growth in most ecological environments. The functioning of G-proteins and activated downstream signaling during salt stress is well established and different G-protein subunits and a few downstream effectors have been identified. Arabidopsis G-protein ß-subunit (AGB1) regulates the movement of Na+ from roots to shoots along with a significant role in controlling Na+ fluxes in roots, however, the molecular mechanism of AGB1 mediated salt stress regulation is not well understood. Here, we report the comparative proteome profiles of Arabidopsis AGB1 null mutant agb1-2 to investigate how the absence of AGB1 modulates the protein repertoire in response to salt stress. High-resolution two-dimensional gel electrophoresis (2-DE) showed 27 protein spots that were differentially modulated between the control and NaCl treated agb1-2 seedlings of which seven were identified by mass spectrometry. Functional annotation and interactome analysis indicated that the salt-responsive proteins were majorly associated with cellulose synthesis, structural maintenance of chromosomes, DNA replication/repair, organellar RNA editing and indole glucosinolate biosynthesis. Further exploration of the functioning of these proteins could serve as a potential stepping stone for dissection of molecular mechanism of AGB1 functions during salt stress and in long run could be extrapolated to crop plants for salinity stress management.

Emerging concern of nano-pollution in agro-ecosystem: Flip side of nanotechnology.

Nanomaterials (NMs) have proven to be a game-changer in agriculture, showcasing their potential to boost plant growth and safeguarding crops. The agricultural sector has widely adopted NMs, benefiting from their small size, high surface area, and optical properties to augment crop productivity and provide protection against various stressors. This is attributed to their unique characteristics, contributing to their widespread use in agriculture. Human exposure from various components of agro-environmental sectors (soil, crops) NMs residues are likely to upsurge with exposure paths may stimulates bioaccumulation in food chain. With the aim to achieve sustainability, nanotechnology (NTs) do exhibit its potentials in various domains of agriculture also have its flip side too. In this review article we have opted a fusion approach using bibliometric based analysis of global research trend followed by a holistic assessment of pros and cons i.e. toxicological aspect too. Moreover, we have also tried to analyse the current scenario of policy associated with the application of NMs in agro-environment.

Engineered nanomicelles targeting proliferation and angiogenesis inhibit tumour progression by impairing the synthesis of ceramide-1-phosphate.

Tumour cells secrete various proangiogenic factors like VEGF, PDGF, and EGF that result in the formation of highly vascularized tumours with an immunosuppressive tumour microenvironment. As tumour growth and metastasis are highly dependent on angiogenesis, targeting tumour vasculature along with rapidly dividing tumour cells is a potential approach for cancer treatment. Here, we specifically engineered sub-100 sized nanomicelles (DTX-CA4 NMs) targeting proliferation and angiogenesis using an esterase-sensitive phosphocholine-tethered docetaxel conjugate of lithocholic acid (LCA) (PC-LCA-DTX) and a poly(ethylene glycol) (PEG) derivative of an LCA-combretastatin A4 conjugate (PEG-LCA-CA4). DTX-CA4 NMs effectively inhibit the tumour growth in syngeneic (CT26) and xenograft (HCT116) colorectal cancer models, inhibit tumour recurrence, and enhance the percentage survival in comparison with individual drug-loaded NMs. DTX-CA4 NMs enhance the T cell-mediated anti-tumour immune response and DTX-CA4 NMs in combination with an immune checkpoint inhibitor, anti-PDL1 antibody, enhance the anti-tumour response. We additionally showed that DTX-CA4 NMs effectively attenuate the production of ceramide-1-phosphate, a key metabolite of the sphingolipid pathway, by downregulating the expression of ceramide kinase at both transcriptional and translational levels. Therefore, this study presents the engineering of effective DTX-CA4 NMs for targeting the tumour microenvironment that can be explored further for clinical applications.

Therapeutic potential and pharmacological mechanism of visnagin.

Visnagin is a furanochromone and one of the most important compound in the Ammi visnaga (L.) Lam (a synonym of Visnaga daucoides Gaertn.) plant, which is used to cure various ailments. Many investigations into the bioactive properties of visnagin have been studied to date. The literature on visnagin demonstrates its biological properties, including anti-inflammatory, anti-diabetic, and beneficial effects in cardiovascular and renal diseases. Moreover, visnagin improves sperm quality parameters, stimulates steroidogenesis, and increases serum gonadotropins and testosterone levels, while decreasing pro-inflammatory cytokines, oxidative damage, genomic instability, and it modulates apoptosis. Thus, visnagin has emerged as an exciting lead for further research, owing to its potential in various unmet clinical needs. The current review summarized its basic structure, pharmacokinetics, and pharmacological effects, focusing on its mechanisms of action. The review will help to understand the potential of visnagin as an alternative treatment strategy for several diseases and provide insight into research topics that need further exploration for visnagin's safe clinical use. Please cite this article as: Yadav P, Singh SK, Datta S, Verma S, Verma A, Rakshit A, Bali A, Bhatti JS, Khurana A, Navik U. Therapeutic potential and pharmacological mechanism of visnagin. J Integr Med. 2024; Epub ahead of print.

Betaine ameliorates doxorubicin-induced cardiomyopathy by inhibiting oxidative stress, inflammation, and fibrosis through the modulation of AMPK/Nrf2/TGF-ß expression.

Doxorubicin (DOX) is a broad-spectrum antibiotic with potent anti-cancer activity. Nevertheless, despite having effective anti-neoplasm activity, its use has been clinically restricted due to its life-threatening side effects, such as cardiotoxicity. It is evident that betaine has anti-oxidant, and anti-inflammatory activity and has several beneficial effects, such as decreasing the amyloid-ß generation, reducing obesity, improving steatosis and fibrosis, and activating AMP-activated protein kinase (AMPK). However, whether betaine could mitigate DOX-induced cardiomyopathy is still unexplored. Cardiomyopathy was induced in male Sprague Dawley rats using DOX (4 mg/kg dose with a cumulative dose of 20 mg/kg, i.p.). Further, betaine (200 and 400 mg/kg) was co-treated with DOX through oral gavage for 28 days. After the completion of the study, several biochemical, oxidative stress parameters, histopathology, western blotting, and qRT-PCR were performed. Betaine treatment significantly reduced CK-MB, LDH, SGOT, and triglyceride levels, which are associated with cardiotoxicity. DOX-induced increased oxidative stress was also mitigated by betaine intervention as the SOD, catalase, MDA, and nitrite levels were restored. The histopathological investigation also confirmed the cardioprotective effect of betaine against DOX-induced cardiomyopathy as the tissue injury was reversed. Further, molecular analysis revealed that betaine suppressed the DOX-induced increased expression of phospho-p53, phospho-p38 MAPK, NF-kB p65, and PINK 1 with an upregulation of AMPK and downregulation of Nrf2 expression. Interestingly, qRT-PCR experiments show that betaine treatment alleviates the DOX-induced increase in inflammatory (TNF-α, NLRP3, and IL-6) and fibrosis (TGF-ß and Acta2) related gene expression, halting the cardiac injury. Interestingly, betaine also improves the mRNA expression of Nrf2, thus modulating the expression of antioxidant proteins and preventing oxidative damage. Here, we provide the first evidence that betaine treatment prevents DOX-induced cardiomyopathy by inhibiting oxidative stress, inflammation, and fibrosis by regulating AMPK/Nrf2/TGF-ß expression. We believe that betaine can be utilized as a potential novel therapeutic strategy for preventing DOX-induced cardiotoxicity.

Engineered nanomicelles inhibit the tumour progression via abrogating the prostaglandin-mediated immunosuppression.

Cancer treatment is challenged due to immunosuppressive inflammatory tumour microenvironment (TME) caused by infiltration of tumour-promoting and inhibition of tumour-inhibiting immune cells. Here, we report the engineering of chimeric nanomicelles (NMs) targeting the cell proliferation using docetaxel (DTX) and inflammation using dexamethasone (DEX) that alters the immunosuppressive TME. We show that a combination of phospholipid-DTX conjugate and PEGylated-lipid-DEX conjugate can self-assemble to form sub-100 nm chimeric NMs (DTX-DEX NMs). Anti-cancer activities against syngeneic and xenograft mouse models showed that the DTX-DEX NMs are more effective in tumour regression, enhance the survival of mice over other treatment modes, and alter the tumour stroma. DTX-DEX NMs cause a significant reduction in myeloid-derived suppressor cells, alter the polarization of macrophages, and enhance the accumulation of cytotoxic CD4+ and CD8+ T cells in tumour tissues, along with alterations in cytokine expression. We further demonstrated that these DTX-DEX NMs inhibit the synthesis of prostaglandins, especially PGE2, by targeting the cyclooxygenase 2 that is partly responsible for immunosuppressive TME. Therefore, this study presents, for the first time, the engineering of lithocholic acid-derived chimeric NMs that affect the prostaglandin pathway, alter the TME, and mitigate tumour progression with enhanced mice survival.

Radiomics-enhanced early regression index for predicting treatment response in rectal cancer: a multi-institutional 0.35 T MRI-guided radiotherapy study.

PURPOSE: The accurate prediction of treatment response in locally advanced rectal cancer (LARC) patients undergoing MRI-guided radiotherapy (MRIgRT) is essential for optimising treatment strategies. This multi-institutional study aimed to investigate the potential of radiomics in enhancing the predictive power of a known radiobiological parameter (Early Regression Index, ERITCP) to evaluate treatment response in LARC patients treated with MRIgRT. METHODS: Patients from three international sites were included and divided into training and validation sets. 0.35 T T2*/T1-weighted MR images were acquired during simulation and at each treatment fraction. The biologically effective dose (BED) conversion was used to account for different radiotherapy schemes: gross tumour volume was delineated on the MR images corresponding to specific BED levels and radiomic features were then extracted. Multiple logistic regression models were calculated, combining ERITCP with other radiomic features. The predictive performance of the different models was evaluated on both training and validation sets by calculating the receiver operating characteristic (ROC) curves. RESULTS: A total of 91 patients was enrolled: 58 were used as training, 33 as validation. Overall, pCR was observed in 25 cases. The model showing the highest performance was obtained combining ERITCP at BED = 26 Gy with a radiomic feature (10th percentile of grey level histogram, 10GLH) calculated at BED = 40 Gy. The area under ROC curve (AUC) of this combined model was 0.98 for training set and 0.92 for validation set, significantly higher (p = 0.04) than the AUC value obtained using ERITCP alone (0.94 in training and 0.89 in validation set). CONCLUSION: The integration of the radiomic analysis with ERITCP improves the pCR prediction in LARC patients, offering more precise predictive models to further personalise 0.35 T MRIgRT treatments of LARC patients.

Out of field scatter from electron applicator in modern linear accelerators.

BACKGROUND: Electron out-of-field scatter is generally not given importance mainly in electron fields. However, this is important when applicator down and boost treatments are given usually at an angle from the central axis. The electron scatter dose is found to be far away from the central axis which could be easily ignored. PURPOSE: This study aims to investigate the out-of-field radiation doses from electron applicators and their effects on clinical treatment. By identifying the parameters that contribute to out-of-field doses and to explore potential strategies for reducing these doses in order to improve patient outcomes from modern machines. METHODS: Measurements were performed in water phantom using electron diode for modern Elekta and Varian machines. Dose profiles were acquired at surface and dmax with 0° and 90° collimation angle. Various gantry angles were also studied for some data with IC Profiler. The profiles were normalized with respect to the central axis dose. RESULTS: The scatter dose peaks were found at a distance between 11 and 28 cm from the central axis on all machines. However, the peak shifts to 15 cm at 90° collimator when beam is tilted. The position and intensity of the dose varies with depth, collimator, and gantry angles for both Elekta and Varian machines. Due to clearance issues more gantry angles were studied for Elekta applicator compared to Varian. In general, Varian TrueBeam has a lower scatter that Elekta Infinity. The 90° collimator angle has a higher scatter compared to zero degree for both machines. CONCLUSIONS: There are clinically significant peripheral doses around 3% of the central axis dose from the electron applicator. Elekta has a slightly higher scatter (3%) than Varian (2%) that peaks at 25 cm which is clinically important but often overlooked.

Beam quality correction factors for ionization chambers in a 0.35 T magnetic resonance (MR)-linac - A Monte Carlo study.

PURPOSE: The purpose of this study was to directly calculate [Formula: see text] correction factors for four cylindrical ICs for a 0.35 T MR-linac using the Monte Carlo (MC) method. METHODS: A previously-validated TOPAS/GEANT4 MC head model of the 0.35 T MR-linac was employed. The MR-compatible Exradin A12, A1SL, A26, and A28 cylindrical ICs were modeled considering the dead volume in the air cavity. The [Formula: see text] correction factor was determined for initial electron energies of 5-7 MeV. The correction factor was calculated for all four angular orientations in the lateral plane. The impact of the 0.35 T magnetic field on the IC response was also investigated. RESULTS: The maximum beam quality dependence in the [Formula: see text] exhibited by the A12, A1SL, A26, and A28 ICs was 1.10 %, 2.17 %, 0.81 %, and 1.75 %, respectively, considering all angular orientations. The magnetic field dependence was < 1 % and the maximum [Formula: see text] correction was < 2 % when the detector was aligned along the direction of the magnetic field at 0° and 180° angles. The A12 IC over-responded up to 5.40 % for the orthogonal orientation. An asymmetry in the response of up to 8.30 % was noted for the A28 IC aligned at 90° and 270° angles. CONCLUSIONS: A parallel orientation for the IC, with respect to the magnetic field, is recommended for reference dosimetry in MRgRT. Both over and under-response in the IC signal was noted for the orthogonal orientations, which is highly dependent on the cavity diameter, cavity length, and the dead volume.

Sustainable water management in rice cultivation reduces arsenic contamination, increases productivity, microbial molecular response, and profitability.

Arsenic (As) and silicon (Si) are two structurally competitive natural elements where Si minimises As accumulation in rice plants, and based on this two-year field trial, the study proposes adopting alternating wetting and drying (AWD) irrigation as a sustainable water management strategy allowing greater Si availability. This field-based project is the first report on AWD's impact on As-Si distribution in fluvio-alluvial soils of the entire Ganga valley (24 study sites, six divisions), seasonal variance (pre-monsoon and monsoon), rice plant anatomy and productivity, soil microbial diversity, microbial gene ontology profiling and associated metabolic pathways. Under AWD to flooded and pre-monsoon to monsoon cultivations, respectively, greater Si availability was achieved and As-bioavailability was reduced by 8.7 ± 0.01-9.2 ± 0.02% and 25.7 ± 0.09-26.1 ± 0.01%. In the pre-monsoon and monsoon seasons, the physiological betterment of rice plants led to the high rice grain yield under AWD improved by 8.4 ± 0.07% and 10.0 ± 0.07%, proving the economic profitability. Compared to waterlogging, AWD evidences as an optimal soil condition for supporting soil microbial communities in rice fields, allowing diverse metabolic activities, including As-resistance, and active expression of As-responsive genes and gene products. Greater expressions of gene ontological terms and complex biochemical networking related to As metabolism under AWD proved better cellular, genetic and environmental responsiveness in microbial communities. Finally, by implementing AWD, groundwater usage can be reduced, lowering the cost of pumping and field management and generating an economic profit for farmers. These combined assessments prove the acceptability of AWD for the establishment of multiple sustainable development goals (SDGs).

Role of buccal fat pad to reduce the chances of re-ankylosis-A systematic review of literature.

The role of buccal fat pad (BFP) as interpositional material in the temporomandibular joint ankylosis (TMJA) have been well documented. The purpose of the present systematic review is to reinforce the role of buccal fat pad as interpositional material in preventing re-ankylosis. A systematic search was conducted in PubMed, Google Scholar, Semantic scholar and Cochrane library database from 1980 to 2022 following the PRISMA guidelines. The studies using BFP as interpositional material in TMJA with more than 10 patients with atleast a follow-up of 6-months were included. All the human studies {prospective, retrospective, case reports/series (with more than 10 subjects), randomized or non-randomized trial) reporting the outcome of BFP as interpositional material were included. The present systematic review included 11 studies (prospective=7, Retrospective=3 and ambispective=1) using BFP as interpositional material. The total number of patients were 205. The number of unilateral TMJA and bilateral TMJA were 153 and 52 respectively, making a number of joint to 257. The distribution of gender was almost equal (few studies did not report the gender distribution). The minimum follow-up was 6-months and extended up to 5.3 years. Out of 205 patients, no re-ankylosis was reported in patients. The authors concluded that the BFP is nearly ideal and a preferred interpositional material to prevent re-ankylosis in temporomandibular joint ankylosis. Its vicinity to TMJ, ease of harvesting through the same surgical site and avoiding other scar makes it a preferred interpositional material in TMJA cases.

A multicenter study of modified electron beam output calibration.

PURPOSE: This study aims to assess the accuracy of a modified electron beam calibration based on the IAEA TRS-398 and AAPM-TG-51 in multicenter radiotherapy. METHODS: This study was performed using the Elekta and Varian Linear Accelerator electron beams with energies of 4-22 MeV under reference conditions using cylindrical (PTW 30013, IBA FC65-G, and IBA FC65-P) and parallel-plate (PTW 34045, PTW 34001, and IBA PPC-40) chambers. The modified calibration used a cylindrical chamber and an updated k ' Q $k{^{\prime}}_Q$ based on Monte Carlo calculations, whereas TRS-398 and TG-51 used cylindrical and parallel-plate chambers for reference dosimetry. The dose ratio of the modified calibration procedure, TRS-398 and TG-51 were obtained by comparing the dose at the maximum depth of the modified calibration to TRS-398 and TG-51. RESULTS: The study found that all cylindrical chambers' beam quality conversion factors determined with the modified calibration ( k ' Q ) $( {{{k^{\prime}}}_Q} )$ to the TRS-398 and TG-51 vary from 0.994 to 1.003 and 1.000 to 1.010, respectively. The dose ratio of modified/TRS-398cyl and modified/TRS-398parallel-plate, the variation ranges were 0.980-1.014 and 0.981-1.019, while for the counterpart modified/TG-51cyl was found varying between 0.991 and 1.017 and the ratio of modified/TG-51parallel-plate varied in the range of 0.981-1.019. CONCLUSION: This multi-institutional study analyzed a modified calibration procedure utilizing new data for electron beam calibrations at multiple institutions and evaluated existing calibration protocols. Based on observed variations, the current calibration protocols should be updated with detailed metrics on the stability of linac components.

Characteristics of a plastic scintillation detector in photon beam dosimetry.

BACKGROUND: Plastic scintillating detectors (PSD) have gained popularity due to small size and are ideally suited in small-field dosimetry due to no correction needed and hence detector reading can be compared to dose. Likewise, these detectors are active and water equivalent. A new PSD from Blue Physics is characterized in photon beam. PURPOSE: Innovation in small-field dosimetry detector has led us to examine Blue Physics PSD (BP-PSD) for use in photon beams from linear accelerator. METHODS: BP-PSD was acquired and its characteristics were evaluated in photon beams from a Varian TrueBeam. Data were collected in a 3D water tank. Standard parameters; dose, dose rate, energy, angular dependence and temperature dependence were studied. Depth dose, profiles and output in a reference condition as well as small fields were measured. RESULTS: BP-PSD is versatile and provides data very similar to an ion chamber when Cerenkov radiation is properly accounted. This device measures data pulse by pulse which very few detectors can perform. The differences between ion chamber data and PSD are < 2% in most cases. The angular dependence is a bit pronounces to 1.5% which is due to PSD housing. Depth dose and profiles are comparable within < 1% to an ion chamber. For small fields this detector provides suitable field output factor compared to other detectors and Monte Carlo (MC) simulated data without any added correction factor. CONCLUSIONS: The characteristics of Blue Physics PSD is uniquely suitable in photon beam and more so in small fields. The data are reproducible compared to ion chamber for most parameters and ideally suitable for small-field dosimetry without any correction factor.

Betaine alleviates doxorubicin-induced nephrotoxicity by preventing oxidative insults, inflammation, and fibrosis through the modulation of Nrf2/HO-1/NLRP3 and TGF-ß expression.

Doxorubicin (Dox) is an anthracycline antibiotic used to treat various cancers and shows severe toxicity in multiple organ systems, including kidneys. Evidence shows that betaine's antioxidant and anti-inflammatory properties could prevent the onset of several disorders. Hence, the present study aims to investigate the therapeutic potential of betaine on Dox-induced nephrotoxicity (DIN). Nephrotoxicity was induced in male Sprague Dawley rats using Dox at a dose of 4 mg/kg (cumulative dose: 20 mg/kg) by the intraperitoneal route and cotreated with betaine through oral gavage (200 and 400 mg/kg) for 28 days. At the end of the experiment, biochemical, oxidative stress parameters, histopathology, and qRT-PCR were performed. DIN was indicated by elevated serum creatinine, urea, and decreased albumin levels representing kidney damage; the histopathological lesions (increased capsular space, renal tubule damage, and fibrosis) in renal tissues supported these biochemical findings. Interestingly, betaine treatment improves these alterations in Dox-treated rats. Further, betaine treatment decreases the lipid peroxidation and nitrite concentration and increases the superoxide dismutases and catalase enzyme concentration in Dox-treated rats. Fascinatingly, at the molecular level, DIN in rats shows upregulation of the Nrf2/HO-1 gene, while betaine treatment attenuated its expression along with the downregulation of inflammatory genes (NLRP3, TLR-4, TNF-α, and IL-6) and fibrosis-related genes (TGF-ß and Acta2) expression in Dox-treated rats. These results showed that betaine has reno-protective properties by reducing inflammatory and fibrotic mediators and enhancing antioxidant capacity in the renal tissue of rats treated with Dox. We believe betaine can be exploited as a dietary supplement to attenuate DIN.

Therapeutic potential of stem cells in regeneration of liver in chronic liver diseases: Current perspectives and future challenges.

The deposition of extracellular matrix and hyperplasia of connective tissue characterizes chronic liver disease called hepatic fibrosis. Progression of hepatic fibrosis may lead to hepatocellular carcinoma. At this stage, only liver transplantation is a viable option. However, the number of possible liver donors is less than the number of patients needing transplantation. Consequently, alternative cell therapies based on non-stem cells (e.g., fibroblasts, chondrocytes, keratinocytes, and hepatocytes) therapy may be able to postpone hepatic disease, but they are often ineffective. Thus, novel stem cell-based therapeutics might be potentially important cutting-edge approaches for treating liver diseases and reducing patient' suffering. Several signaling pathways provide targets for stem cell interventions. These include pathways such as TGF-ß, STAT3/BCL-2, NADPH oxidase, Raf/MEK/ERK, Notch, and Wnt/ß-catenin. Moreover, mesenchymal stem cells (MSCs) stimulate interleukin (IL)-10, which inhibits T-cells and converts M1 macrophages into M2 macrophages, producing an anti-inflammatory environment. Furthermore, it inhibits the action of CD4+ and CD8+ T cells and reduces the activity of TNF-α and interferon cytokines by enhancing IL-4 synthesis. Consequently, the immunomodulatory and anti-inflammatory capabilities of MSCs make them an attractive therapeutic approach. Importantly, MSCs can inhibit the activation of hepatic stellate cells, causing their apoptosis and subsequent promotion of hepatocyte proliferation, thereby replacing dead hepatocytes and reducing liver fibrosis. This review discusses the multidimensional therapeutic role of stem cells as cell-based therapeutics in liver fibrosis.

Selenium - An environmentally friendly micronutrient in agroecosystem in the modern era: An overview of 50-year findings.

Agricultural productivity is constantly being forced to maintain yield stability to feed the enormously growing world population. However, shrinking arable and nutrient-deprived soil and abiotic and biotic stressor (s) in different magnitudes put additional challenges to achieving global food security. Though well-defined, the concept of macro, micronutrients, and beneficial elements is from a plant nutritional perspective. Among various micronutrients, selenium (Se) is essential in small amounts for the life cycle of organisms, including crops. Selenium has the potential to improve soil health, leading to the improvement of productivity and crop quality. However, Se possesses an immense encouraging phenomenon when supplied within the threshold limit, also having wide variations. The supplementation of Se has exhibited promising outcomes in lessening biotic and abiotic stress in various crops. Besides, bulk form, nano-Se, and biogenic-Se also revealed some merits and limitations. Literature suggests that the possibilities of biogenic-Se in stress alleviation and fortifying foods are encouraging. In this article, apart from adopting a combination of a conventional extensive review of the literature and bibliometric analysis, the authors have assessed the journey of Se in the "soil to spoon" perspective in a diverse agroecosystem to highlight the research gap area. There is no doubt that the time has come to seriously consider the tag of beneficial elements associated with Se, especially in the drastic global climate change era.

Efficacy of prokinetic agents in diabetic gastroparesis comparing symptomatology and scintigraphy - An open-label trial.

Background: It is pertinent to objectively assess the severity of diabetic gastroparesis and tailor treatment accordingly. The current study was planned to document gastroparesis by gastric emptying scintigraphy (GES) objectively and see the effect of medications and diet control on clinical and GES after four weeks. Methods: A prospective, open-label randomized trial was conducted in the Department of Internal Medicine at a tertiary care teaching hospital over twelve months. Type 2 diabetic patients aged 18-65 years diagnosed with a case of delayed gastric emptying by gastric scintigraphy were included. All baseline GSCI was recorded, and then they were allotted to 3 groups - Group-1 (Levosulpiride 25mg once daily), group-2 (Cinitapride 1mg thrice daily), and Group-3 (Waitlisted control) by block randomization and followed-up weekly till four weeks. After four weeks duration, if not improved clinically, then Group-3 on diet and diabetic control only, were randomized into Levosulpiride 25mg once daily (Group 1), and Cinitapride 1mg Thrice daily (Group 2) for the next four weeks. Results: Forty confirmed cases with diabetic gastroparesis documented by Gastroparesis Symptom Cardinal Index (GCSI) scoring and later by Scintigraphy (GES) were included in this study. However, there was no statistically significant difference between the Levosulpiride and Cinitapride groups when all symptoms were taken into account. Levosulpiride was significantly more effective than Cinitapride in improving individual symptoms like nausea, vomiting, stomach fullness, and early satiety. Conclusion: Levosulpiride is better than Cinitapride in improving the symptoms of diabetic gastroparesis but no significant effect on gastric scintigraphy.

Evaluation of efficacy of non-coding RNA in abiotic stress management of field crops: Current status and future prospective.

Abiotic stresses are responsible for the major losses in crop yield all over the world. Stresses generate harmful ROS which can impair cellular processes in plants. Therefore, plants have evolved antioxidant systems in defence against the stress-induced damages. The frequency of occurrence of abiotic stressors has increased several-fold due to the climate change experienced in recent times and projected for the future. This had particularly aggravated the risk of yield losses and threatened global food security. Non-coding RNAs are the part of eukaryotic genome that does not code for any proteins. However, they have been recently found to have a crucial role in the responses of plants to both abiotic and biotic stresses. There are different types of ncRNAs, for example, miRNAs and lncRNAs, which have the potential to regulate the expression of stress-related genes at the levels of transcription, post-transcription, and translation of proteins. The lncRNAs are also able to impart their epigenetic effects on the target genes through the alteration of the status of histone modification and organization of the chromatins. The current review attempts to deliver a comprehensive account of the role of ncRNAs in the regulation of plants' abiotic stress responses through ROS homeostasis. The potential applications ncRNAs in amelioration of abiotic stresses in field crops also have been evaluated.