Effect of boron fertilization on productivity and sustainability of rice-wheat cropping system in Tarai region, North-West India.

Extensive global dependency on rice and wheat crops has necessitated the adoption of intensive cultivation practices, thereby compelling to closely monitor the potential yield-limiting factors, among which, boron (B) deficiency stands out to be a prime concern. The present study explores the effects of B fertilization strategies within the Rice-Wheat Cropping System (RWCS) in the Tarai region of North-West India. A comprehensive six-year field experiment was conducted (2013-2019) at G.B. Pant University of Agriculture and Technology, Uttarakhand, India. The experiment tested graded B doses (0.5, 1.0, 1.5, and 2.0 kg ha-1) at varied frequencies (single, alternate, and annual) in a factorial design. The study revealed significant impacts of alternate B application at 1.5 kg ha-1 on crop yields and the Sustainable Yield Index (SYI). The System Rice Equivalent Yield (SREY) exhibited an increase of 6.7% with B supplementation over B-deprived plots, highlighting the pivotal role of B fertilizer in enhancing productivity within the RWCS. The economic optimum B dose was found to be 1.422 kg ha-1 using a linear plus plateau model, resulting in a calculated annual SREY of 9.73 t ha-1 when applied alternately to the cropping system. Continuous application and higher B rates demonstrated substantial increases in various B fractions, while the mobility factor remained within 10%, depicting safe ecological limits. The distribution of fractions in B-treated plots on average followed the order: residual B > organically-bound B > oxide bound B > specifically adsorbed B > readily soluble B. Similarities in the distribution patterns of B fractions between B-treated plots and the control indicated potential influence of biotic or abiotic processes on B fraction dynamics, even in the absence of external B application. To sum up, B application in alternate years at 1.5 kg ha-1 was most sustainable in enhancing the SREY, SYI, available soil B, and B fractions and lowering the environmental hazards.

Ameliorative effects of gallic acid on GLUT-4 expression and insulin resistance in high fat diet-induced obesity animal model mice, Mus musculus.

Reduced activity of glucose transporter type 4 isoform (GLUT-4), an insulin-sensitive glucose transporter distributed on the adipocytes, is associated with impaired insulin signaling. Insulin resistance resulting from alteration in glucose transport is responsible for exacerbating the emergence of metabolic abnormalities. The present study aimed to investigate the effects of the antidote gallic acid (GA) on expression-related changes in GLUT-4 and insulin receptor substrate-1 (IRS-1) in the visceral adipose tissue and on the subsequent development of insulin resistance in a high-fat diet (HFD)-induced obesity animal model. Methods: Twenty-four female Swiss albino mice were used and separated into the following four groups (six animals in each group): control group (standard pellet diet), HFD group, (60% HFD), HFD + GA group (60% HFD and GA 50 mg/kg body weight for 60 days), and GA group (GA 50 mg/kg body weight for 60 days). The effect of HFD on serum glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL), low-density lipoprotein (LDL) cholesterol, and insulin was evaluated. Additionally, homeostasis model assessment for insulin resistance (HOMA-IR) and glucose tolerance test (GTT) was performed. The serum antioxidative profile, which comprises oxidative parameters (superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase [GPx]) was measured. The effectiveness of GA against HFD-induced alteration in GLUT-4 and IRS-1 expression was also evaluated. Results: The experimental group that fed on GA + HFD had improved levels of serum triglycerides (p˂0.001), cholesterol (p˂0.05), and LDL cholesterol. GA administration also significantly improved hyperinsulinemia and HOMA-IR index (p˂0.001) in HFD mice. GA improved GTT results (p˂0.05); activity of SOD, CAT, and GPx (p˂0.05); and upregulated mRNA expression of GLUT-4 and IRS-1(p˂0.05) in the visceral adipose tissue in the HFD + GA experimental group. Conclusion: A link exists between insulin resistance, GLUT-4, and IRS-1 expression in the adipose tissue, and the initiation of metabolic syndrome, a condition characterized by obesity. GA may promote insulin signaling, glucose uptake, and lipid metabolism in the adipose tissues by mitigating oxidative stress. GA can also be used to manage obesity-related comorbidities including type 2 diabetes and dyslipidemia. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01194-5.

Therapeutic Role of Phytophenol Gallic Acid for the Cure of COVID-19 Pathogenesis.

The SARS CoV-2 virus, the causative agent of COVID-19 uses the ACE-2 receptor of the host to penetrate and infect the cell, mainly in the pulmonary, renal, and cardiac tissues. The earlier reported Delta and the recent Omicron are the variants of concern. The mutations in the RBD region of spike protein are associated with increased RBD-ACE-2 receptor interaction. This binding affinity between spike protein and the receptor is greater in Omicron than in the Delta variant. Moreover, the Omicron variant has numerous hydrophobic amino acids in the RBD region of the spike protein, which maintain its structural integrity. Gallic acid is a phytophenol and shows high binding affinity toward the ACE-2 receptors, which may be helpful for better outcomes in the treatment of COVID-19 pathogenesis. In the present study, significant data were collected from different databases i.e., PubMed, Scopus, Science Direct, and Web of Science by using keywords like anti-oxidative, anti-inflammatory, and antimicrobial properties of gallic acid, in addition to receptor-based host cell interaction of SARS CoV-2 virus. The finding shows that gallic acid can reduce inflammation by attenuating NF-κB and MAPK signaling pathways to suppress the release of ICAM-1, a cell surface glycoprotein; various pro-inflammatory cytokines like TNF-α, IL 1-ß, IL-6, IL-10, and chemokines like CCL-2,5, CXCL-8 along with tissue infiltration by immune cells. The purpose of this review is to highlight the therapeutic potential of gallic acid in COVID-19 pathogenesis based on its strong anti-oxidative, anti-inflammatory, and anti- microbial properties.

Effects of oxytocin and antagonist antidote atosiban on body weight and food intake of female mice, Mus musculus.

Growing evidence suggests that oxytocin (OT) plays an important factor for the control of food intake, body weight, and energy metabolism in human and non-human animals. It has reported previously, the downregulation in oxytocin receptors (OTRs) expression is linked with the development of obesity, but exogenous OT reverse body weight and food intake in obese animal model. It is important to know that, whether intraperitoneal administration crosses blood brain barrier. Therefore, in the present experiment, we study the impact of intraperitoneal administration of synthetic OT 0.0116 mg/kg and antagonist atosiban (OTA) 1 mg/kg on food intake, and body weight of female mice, Mus musculus for different duration i.e. 30, 60, and 90 days. In this study, it was observed that there was significant decrease (p<0.001, one-way analysis of variance [ANOVA]) in the body weight (BW), food intake, and gonadosmatic indices (GSI) after the intraperitoneal exposure of OT at dose 0.0116 mg/kg up to 90 days and inhibits via antagonist atosiban. These results indicates that intraperitoneal administration of OT can be used for treatment for longer duration without any side effects and maintains homeostasis in physiologic system regulates body weight and gonadal weight in female mice, which represent an important therapeutic tool for the obesity and metabolic disorder in female.

Effectiveness of dietary diabetes insipidus bundle on the severity of postoperative fluid imbalance in pituitary region tumours: A randomized controlled trial.

AIM: To test the effectiveness of nurse-led dietary diabetes insipidus (DI) bundle on the severity of postoperative fluid imbalance in pituitary region tumours. DESIGN: Blinded randomized controlled trial. METHODS: Patients aged 18-65 operated for sellar-suprasellar tumours in an Indian tertiary care centre were enrolled through total enumeration sampling and underwent randomization with allocation concealment during Sep 2018-Feb 2019. Pre-operative DI, postoperative ventilation, renal failure or decompensated diabetes mellitus were excluded. Patients in the intervention group received a nurse-led DI bundle (validated by three Delphi rounds) with four dietary components: intake of only water during thirst and avoidance of the following-added salt, high-protein foods and caffeinated drinks. Treating clinicians and the investigator assessing outcome were blinded about enrolment. Urine output, serum sodium, vasopressin requirement and hospital stay were assessed as primary outcomes. The outcome measures were monitored daily till the 6th postoperative day. Analyses were performed on 'intention-to-treat' basis, irrespective of compliance. Independent t-test and Chi-square test were used. RESULTS: Of the initial 63 patients, 50 fulfilling criteria were randomized to two groups and assessed over six days yielding 150 patient-days per group. There were no significant baseline differences between groups. The mean daily urine output was significantly lower in the DI bundle group than in control, both overall and among endonasal operated pituitary adenomas [3000.09(462.7) vs. 4095.71(896.4)ml & 2987.14(419.5) vs. 4064.73(1051)ml], with the greatest difference on the second postoperative day. Though hypernatraemia in controls became most prominent during days 2-3 and resolved in a week, it was significantly lower in the intervention group (12.7% vs. 30.7% overall, 11.4% vs. 29.4% endonasal adenomas). The need for vasopressin analogues and hospital stay were also significantly lower with DI bundle (p < 0.001). CONCLUSION: This is probably the first ever report of dietary DI bundle among operated pituitary patients, which seem to flatten the DI trend with significant benefits in polyuria, hypernatraemia, vasopressin requirement and hospital stay. TRIAL REGISTRATION: CTRI/2018/07/015127 of ICMR. IMPACT: The nurse-led dietary DI bundle has effectively reduced the severity of DI among operated pituitary patients with significant benefits in polyuria, hypernatraemia, vasopressin requirement and hospital stay. Its implementation is simple and easy to carry out, especially in resource-constrained institutions, where continuous monitoring and repeated serum sodium estimation are difficult.

Oxytocin as a Potential Adjuvant Against COVID-19 Infection.

This study summarized the benefits of oxytocin in the attenuation of coronavirus disease (COVID-19) pathogenesis. The recent outbreak of COVID-19 has become a pandemic with 7,323,761 infected patients and has created a health emergency worldwide. On the basis of the clinical study, COVID-19 shows homology with other coronavirus pathogenesis, i.e., inflammation, oxidative stress, and hyperactivation of the immune system, resulting in cytokine storm and causing acute lung infection (ALI), acute respiratory distress syndrome (ARDS), and kidney dysfunction. Oxytocin is a peptide of nine amino acids and a well-known anti-inflammatory, anti-oxidant, and immune-modulator, which is protective against ALI/ARDS, nephrotoxicity, sepsis, and ischemia- reperfusion medical condition. Oxytocin is a neuromodulator, effective for stress, anxiety, social behavior, and depression, which may be helpful for better outcomes in patients with COVID-19. Significant data show that oxytocin can be useful in the treatment of COVID-19 pathogenesis. A direct application of OT in COVID-19 is unclear; however, its use in an experimental model and humans has continuously demonstrated its safety, and its use in patients with COVID-19 is predicted to be highly beneficial.

Recapitulation and Reversal of Schizophrenia-Related Phenotypes in Setd1a-Deficient Mice.

SETD1A, a lysine-methyltransferase, is a key schizophrenia susceptibility gene. Mice carrying a heterozygous loss-of-function mutation of the orthologous gene exhibit alterations in axonal branching and cortical synaptic dynamics accompanied by working memory deficits. We show that Setd1a binds both promoters and enhancers with a striking overlap between Setd1a and Mef2 on enhancers. Setd1a targets are highly expressed in pyramidal neurons and display a complex pattern of transcriptional up- and downregulations shaped by presumed opposing functions of Setd1a on promoters and Mef2-bound enhancers. Notably, evolutionarily conserved Setd1a targets are associated with neuropsychiatric genetic risk burden. Reinstating Setd1a expression in adulthood rescues cognitive deficits. Finally, we identify LSD1 as a major counteracting demethylase for Setd1a and show that its pharmacological antagonism results in a full rescue of the behavioral and morphological deficits in Setd1a-deficient mice. Our findings advance understanding of how SETD1A mutations predispose to schizophrenia (SCZ) and point to novel therapeutic interventions.

Effects of exogenous oxytocin and atosiban antagonist on GABA in different region of brain.

Gamma amino butyric acid (GABA) is the primary inhibitory neurotransmitter in the vertebral central nervous system. It functions by altering the membrane conductance of Cl- ions, maintaining the membrane potential close to the resting potential. The hormone oxytocin (OT) has a central action where it acts as a neuromodulatory peptide and exerts its action depending upon the distribution of OT receptors (OTR) in the target site. OTRs are G-protein-coupled receptors (GPCRs) comprising different subunits (Gq, Gi, and Gs). The G- protein isoforms have the ability to activate different pathways, but specific agonists and antagonists may show different affinities to OTRs, depending on the specific G-protein isoform to which they are coupled. It is well documented that OTR distribution varies with age and species and in regions of the brain. In this study, we attempted to observe the impact of OT and atosiban (OTA), an OT antagonist, on GABA levels in different regions of the brain. Study animals were exposed intraperitoneally (i.p.) to normal saline (0.89%), OT 0.0116 mg/kg, and OTA 1 mg/kg in different combinations, for 30days. It was observed that OT and OTA administration modulated GABA levels in different regions of brain, while normal saline had no effect. It may be due to OTR receptor expression in different regions of the brain. This is significant because region-specific expression of different receptors could be important in the development of new drugs targeting specific neuropsychiatric disorders.

Effects of subthalamic deep brain stimulation on blink abnormalities of 6-OHDA lesioned rats.

Parkinson's disease (PD) patients and the 6-hydroxydopamine (6-OHDA) lesioned rat model share blink abnormalities. In view of the evolutionarily conserved organization of blinking, characterization of blink reflex circuits in rodents may elucidate the neural mechanisms of PD reflex abnormalities. We examine the extent of this shared pattern of blink abnormalities by measuring blink reflex excitability, blink reflex plasticity, and spontaneous blinking in 6-OHDA lesioned rats. We also investigate whether 130-Hz subthalamic nucleus deep brain stimulation (STN DBS) affects blink abnormalities, as it does in PD patients. Like PD patients, 6-OHDA-lesioned rats exhibit reflex blink hyperexcitability, impaired blink plasticity, and a reduced spontaneous blink rate. At 130 Hz, but not 16 Hz, STN DBS eliminates reflex blink hyperexcitability and restores both short- and long-term blink plasticity. Replicating its lack of effect in PD patients, 130-Hz STN DBS does not reinstate a normal temporal pattern or rate to spontaneous blinking in 6-OHDA lesioned rats. These data show that the 6-OHDA lesioned rat is an ideal model system for investigating the neural bases of reflex abnormalities in PD and highlight the complexity of PD's effects on motor control, by showing that dopamine depletion does not affect all blink systems via the same neural mechanisms.

Frequency matters: beta-band subthalamic nucleus deep-brain stimulation induces Parkinsonian-like blink abnormalities in normal rats.

The synchronized beta-band oscillations in the basal ganglia-cortical networks in Parkinson's disease (PD) may be responsible for PD motor symptoms or an epiphenomenon of dopamine loss. We investigated the causal role of beta-band activity in PD motor symptoms by testing the effects of beta-frequency subthalamic nucleus deep-brain stimulation (STN DBS) on the blink reflex excitability, amplitude, and plasticity in normal rats. Delivering 16 Hz STN DBS produced the same increase in blink reflex excitability and impairment in blink reflex plasticity in normal rats as occurs in rats with 6-hydroxydopamine lesions and patients with PD. These deficits were not an artifact of STN DBS because, when these normal rats received 130 Hz STN DBS, their blink characteristics were the same as without STN DBS. To demonstrate that the blink reflex disturbances with 16 Hz STN DBS were frequency specific, we tested the same rats with 7 Hz STN DBS, a theta-band frequency typical of dystonia. In contrast to beta stimulation, 7 Hz STN DBS exaggerated the blink reflex plasticity as occurs in focal dystonia. Thus, without destroying dopamine neurons or blocking dopamine receptors, frequency-specific STN DBS can be used to create PD-like or dystonic-like symptoms in a normal rat.