Choline Improves Neonatal Hypoxia-Ischemia Induced Changes in Male but Not Female Rats.

Choline is an essential nutrient with many roles in brain development and function. Supplementation of choline in early development can have long-lasting benefits. Our experiments aimed to determine the efficacy of choline supplementation in a postnatal day (PND) 10 rat model of neonatal hypoxia ischemia (HI) at term using both male and female rat pups. Choline (100 mg/kg) or saline administration was initiated the day after birth and given daily for 10 or 14 consecutive days. We determined choline's effects on neurite outgrowth of sex-specific cultured cerebellar granule cells after HI with and without choline. The magnitude of tissue loss in the cerebrum was determined at 72 h after HI and in adult rats. The efficacy of choline supplementation in improving motor ability and learning, tested using eyeblink conditioning, were assessed in young adult male and female rats. Overall, we find that choline improves neurite outgrowth, short-term histological measures and learning ability in males. Surprisingly, choline did not benefit females, and appears to exacerbate HI-induced changes.

Crosstalk between endoplasmic reticulum stress and anti-viral activities: A novel therapeutic target for COVID-19.

The outbreak of COVID-19 caused by 2019-nCov/SARS-CoV-2 has become a pandemic with an urgent need for understanding the mechanisms and identifying a treatment. Viral infections including SARS-CoV are associated with increased levels of reactive oxygen species, disturbances of Ca++ caused by unfolded protein response (UPR) mediated by endoplasmic reticulum (ER) stress and is due to the exploitation of virus's own protein i.e., viroporins into the host cells. Several clinical trials are on-going including testing Remdesivir (anti-viral), Chloroquine and Hydroxychloroquine derivatives (anti-malarial drugs) etc. Unfortunately, each drug has specific limitations. Herein, we review the viral protein involvement to activate ER stress transducers (IRE-1, PERK, ATF-6) and their downstream signals; and evaluate combination therapies for COVID-19 mediated ER stress alterations. Melatonin is an immunoregulator, anti-pyretic, antioxidant, anti-inflammatory and ER stress modulator during viral infections. It enhances protective mechanisms for respiratory tract disorders. Andrographolide, isolated from Andrographis paniculata, has versatile biological activities including immunomodulation and determining SARS-CoV-2 binding site. Considering the properties of both compounds in terms of anti-inflammatory, antioxidant, anti-pyrogenic, anti-viral and ER stress modulation and computational approaches revealing andrographolide docks with the SARS-CoV2 binding site, we predict that this combination therapy may have potential utility against COVID-19.

Bioremediation of petroleum wastewater by hyper-phenol tolerant Bacillus cereus: Preliminary studies with laboratory-scale batch process.

Petroleum wastewater samples from oil refinery and oil exploration site were treated by hyper phenol-tolerant Bacillus cereus (AKG1 and AKG2) in laboratory-scale batch process to assess their bioremediation efficacy. Quality of the treated wastewater samples were analyzed in terms of removal of chemical oxygen demand (COD), total organic carbon (TOC) and ammonium nitrogen content, and improvement of biological oxygen demand (BOD). Adaptation of these bacteria to the toxic environment through structural changes in their cell membranes was also highlighted. Among different combinations, the co-culture of AKG1 and AKG2 showed the best performance in degrading the wastewater samples.

Isolation and characterization of hyper phenol tolerant Bacillus sp. from oil refinery and exploration sites.

Bacillus cereus MTCC 9817 strain AKG1 and B. cereus MTCC 9818 strain AKG2 were isolated from petroleum refinery and oil exploration site, respectively. The 16S rDNA sequence of strain AKG1 showed the closest relation to B. cereus 99.63% and Bacillus coagulans 99.63% followed by 99.34% homology with Bacillus thuringiensis strain 2PR56-10. AKG2 is mostly related to B. thuringiensis strain CMG 861 with 99.37% homology. The similarity search between AKG1 and AKG2 gave the lowest similarity 99.19% among same genus similar sequences. At phenol concentration of 1000 mg/L, the optimum growth conditions for AKG1 were found to be 37 degrees C and pH 7.0 and the same were found to be 37 degrees C and pH 7.5 for AKG2. The growth kinetics of the strains AKG1 and AKG2 are best fitted by Yano model (maximum growth rate, mu(max)=1.024 h(-1) and inhibition constant, K(I)=171,800 mg/L) and Edward model (mu(max)=0.5969 h(-1) and K(I)=1483 mg/L) respectively. Growth kinetics of both the strains are also well fitted by the Haldane model with mu(max)=0.4396 h(-1) and K(I)=637.8 mg/L for AKG1 and mu(max)=0.9332 h(-1) and K(I)=494.4 mg/L for AKG2.

Hydrogen peroxide-mediated downregulation of matrix metalloprotease-2 in indomethacin-induced acute gastric ulceration is blocked by melatonin and other antioxidants.

Gastric mucosal damage is directly associated with extracellular matrix degradation in which matrix metalloproteinases (MMPs) play a crucial role. Remodeling of connective tissues and loss of tissue integrity due to the action of MMPs are reported in several inflammatory diseases, including gastric ulcer. Indomethacin-induced gastric ulceration involves the generation of reactive oxygen species (ROS) and a reduction in MMP-2 transcription and translation. Our aim was to identify the mechanism for suppression of MMP-2 activity by ROS during acute ulceration and further to examine the possible actions of antioxidants, especially melatonin, during healing. Melatonin (N-acetyl-5-methoxytryptamine) blocked hydroxyl radical and nitrite anion generation, protein oxidation, mucosal cell disruption, and MMP-2 downregulation. In addition, suppression of MMP-2 activity by H2O2 in a dose- and time-dependent manner in vitro is blocked by melatonin, omeprazole, and curcumin. We observed that melatonin and other antioxidants (e.g., curcumin and omeprazole) offered gastroprotection in vivo by upregulation of suppressed MMP-2 expression and activity at the level of secretion and synthesis. Moreover, antioxidants reversed the suppression of MMP-2 expression by upregulation of MT1-MMP and downregulation of TIMP-2. Hence, we hypothesize that antioxidants exerted protection against H2O2-mediated inactivation and downregulation of MMP-2 expression during onset of indomethacin-induced ulceration.