Search

Osmolytes are naturally occurring small molecular weight organic molecules, which are accumulated in large amounts in all life forms to maintain the stability of cellular proteins and hence preserve their functions during adverse environmental conditions. Trimethylamine N-oxide (TMAO) and N,N,N-trimethylglycine (betaine) are methylamine osmolytes that have been extensively studied for their diverse roles in humans and have demonstrated opposing relations with human health. These osmolytes are obtained from food and synthesized endogenously using dietary constituents like choline and carnitine. Especially, gut microbiota plays a vital role in TMAO synthesis and contributes significantly to plasma TMAO levels. The elevated plasma TMAO has been reported to be correlated with the pathogenesis of numerous human diseases, including cardiovascular disease, heart failure, kidney diseases, metabolic syndrome, etc.; Hence, TMAO has been recognized as a novel biomarker for the detection/prediction of several human diseases. In contrast, betaine acts as a methyl donor in one-carbon metabolism, maintains cellular S-adenosylmethionine levels, and protects the cells from the harmful effects of increased plasma homocysteine. Betaine also demonstrates antioxidant and anti-inflammatory activities and has a promising therapeutic value in several human diseases, including homocystinuria and fatty liver disease. The present review examines the multifarious functions of TMAO and betaine with possible molecular mechanisms towards a better understanding of their emerging and diverging functions with probable implications in the prevention, diagnosis, and treatment of human diseases.

Cellular methylamines are osmolytes (low molecular weight organic compounds) believed to offset the urea's harmful effects on the stability and function of proteins in mammalian kidney and marine invertebrates. Although urea and methylamines are found at 2:1 molar ratio in tissues, their opposing effects on protein structure and function have been questioned on several grounds including failure to counteraction or partial counteraction. Here we investigated the possible involvement of cellular salt, NaCl, in urea-methylamine counteraction on protein stability and function. We found that NaCl mediates methylamine counteracting system from no or partial counteraction to complete counteraction of urea's effect on protein stability and function. These conclusions were drawn from the systematic thermodynamic stability and functional activity measurements of lysozyme and RNase-A. Our results revealed that salts might be involved in protein interaction with charged osmolytes and hence in the urea-methylamine counteraction.

Human kidney cells are under constant urea stress due to its urine concentrating mechanism. It is believed that the deleterious effect of urea is counteracted by methylamine osmolytes (glycine betaine and glycerophosphocholine) present in kidney cells. A question arises: Do the stabilizing osmolytes, non-methylamines (myo-inositol, sorbitol and taurine) present in the kidney cells also counteract the deleterious effects of urea? To answer this question, we have measured structure, thermodynamic stability (ΔG D (o)) and functional activity parameters (K m and k cat) of different model proteins in the presence of various concentrations of urea and each non-methylamine osmolyte alone and in combination. We observed that (i) for each protein myo-inositol provides perfect counteraction at 1∶2 ([myo-inositol]:[urea]) ratio, (ii) any concentration of sorbitol fails to refold urea denatured proteins if it is six times less than that of urea, and (iii) taurine regulates perfect counteraction in a protein specific manner; 1.5∶2.0, 1.2∶2.0 and 1.0∶2.0 ([taurine]:[urea]) ratios for RNase-A, lysozyme and α-lactalbumin, respectively.

Missense mutant proteins, such as those produced in individuals with genetic diseases, are often misfolded and subject to processing by intracellular quality control systems. Previously, we have shown using a yeast system that enzymatic function could be restored to I278T cystathionine beta-synthase (CBS), a cause of homocystinuria, by treatments that affect the intracellular chaperone environment. Here, we extend these studies and show that it is possible to restore significant levels of enzyme activity to 17 of 18 (94%) disease causing missense mutations in human cystathionine beta-synthase (CBS) expressed in Saccharomyces cerevisiae by exposure to ethanol, proteasome inhibitors, or deletion of the Hsp26 small heat shock protein. All three of these treatments induce Hsp70, which is necessary but not sufficient for rescue. In addition to CBS, these same treatments can rescue disease-causing mutations in human p53 and the methylene tetrahydrofolate reductase gene. These findings do not appear restricted to S. cerevisiae, as proteasome inhibitors can restore significant CBS enzymatic activity to CBS alleles expressed in fibroblasts derived from homocystinuric patients and in a mouse model for homocystinuria that expresses human I278T CBS. These findings suggest that proteasome inhibitors and other Hsp70 inducing agents may be useful in the treatment of a variety of genetic diseases caused by missense mutations.

Background: Fear of childbirth (FOC) is a feeling of uncertainty and anxiousness before, during or after delivery which may increase the risk of various physical problems and mental disorders thereby affecting maternal and infant morbidity and mortality. Objectives: To estimate the prevalence of fear of childbirth and to determine its associated factors among pregnant women. Methodology: A hospital-based cross-sectional study was conducted among pregnant women attending ante-natal clinic of a tertiary-care hospital in Imphal-East District of Manipur. A 30-item questionnaire was used for data collection. Descriptive statistics, univariate and multivariate logistic regression analysis were performed to test for association taking all variables with p < 0.2 for model building for the adjusted analysis. A p value

Abstract Diabetes, characterized by high blood glucose level, is a progressive metabolic disease that leads to serious health complications. One of the major pathological consequences associated with diabetes is the accumulation of highly reactive carbonyl compounds called advanced glycation end products (AGEs). Most of the AGEs are dicarbonyls and have the potential to covalently modify proteins especially at the lysine residues in a non-enzymatic fashion (a process termed as glycation) resulting in the functional impairment and/or toxic gain in function. Therefore, non-toxic small molecules that can inhibit glycation are of interest for the therapeutic intervention of diabetes. In the present communication, we have investigated the effect of organosulfurs (S-allyl cysteine, SAC and N-acetyl cysteine, NAC) that are major principal components of Allium sativa against the glycation of different proteins. We discovered that both SAC and NAC are potent anti-glycating agents. We also found that both SAC and NAC reduce ROS level and inhibit apoptosis caused by protein glycation.

Abstract Deposition of high-order protein oligomers is a common hallmark of a large number of human diseases and therefore, has been of immense medical interest. From the past several decades, efforts are being made to characterize protein oligomers and explore how they are linked with the disease pathologies. In general, oligomers are non-functional, rather cytotoxic in nature while the functional (non-cytotoxic) oligomers are quite rare. In the present study, we identified new protein oligomers of Ribonuclease-A and Lysozyme that contain functionally active fractions. These functional oligomers are disulfide cross-linked, native-like, and obtained as a result of the covalent modification of the proteins by the toxic metabolite, homocysteine thiolactone accumulated under hyperhomocysteinemia (a condition responsible for cardiovascular complications including atherosclerosis). These results have been obtained from the extensive analysis of the nature of oligomers, functional status, and structural integrity of the proteins using orthogonal techniques. The study implicates the existence of such oligomers as protein sinks that may sequester toxic homocysteines in humans.

Foxtail millet (Setaria italica), an annual grass plant, produces seeds that possess health‐promoting properties owing to its unique protein composition containing a high content of essential amino acids. The mature foxtail seeds mainly consist of proline‐rich, alcohol‐soluble proteins (prolamin) called setarins, comprising about 60% of the total protein, with less content of disulfide cross‐linked proteins than with other cereal and millets. Protein fractionation schemes are an important tool and provide preliminary information on the nature of foxtail proteins for their applications in the field of agriculture, food pharma, and bio‐based materials. Variation in the methods of preparation can influence the composition, structure, and nutritional quality of the protein concentrate. Moreover, foxtail protein or its hydrolysate has shown several bioactive effects that can be explored further for the management of chronic diseases in humans. Additionally, owing to its low cost and excellent functional properties of flour and protein concentrate, foxtail millet can be considered as good candidate for replacing animal protein foods. Furthermore, there is huge potential for successfully developing low‐cost, protein‐rich functional food products helpful in the prevention and management of lifestyle‐related chronic diseases. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

In this study, the effect of ZnO buffer layer on the electrical properties of PbZrTiO3/BiFeO3 (PZT/BFO) multilayers has been reported. For this, PZT/BFO multilayers were spin-coated with and without ZnO buffer layer on platinized silicon wafers. X-ray diffraction results of both the films showed polycrystalline phase pure perovskite structure. Both the films show a dense and homogeneous grain structure. The electric properties of the films were measured. The ZnO buffered multilayer thin film showed ∼3 times improvement in remnant polarization compared to the multilayer thin film with no buffer. The buffered samples were found to have higher dielectric constant (1000 at 100 Hz) compared to that of sample (580 at 100 Hz)) with no buffer. Dielectric constants of both the films were found to be ∼30% tunable at 5 V. The buffered film also showed low leakage current density and higher dielectric breakdown compared to the multilayer thin film without buffer. [ABSTRACT FROM AUTHOR]

Advanced glycation end-products (AGEs; e.g., glyoxal, methylglyoxal or carboxymethyl-lysine) are heterogenous group of toxic compounds synthesized in the body through both exogenous and endogenous pathways. AGEs are known to covalently modify proteins bringing about loss of functional alteration in the proteins. AGEs also interact with their receptor, receptor for AGE (RAGE) and such interactions influence different biological processes including oxidative stress and apoptosis. Previously, AGE-RAGE axis has long been considered to be the maligning factor for various human diseases including, diabetes, obesity, cardiovascular, aging, etc. Recent developments have revealed the involvement of AGE-RAGE axis in different pathological consequences associated with the onset of neurodegeneration including, disruption of blood brain barrier, neuroinflammation, remodeling of extracellular matrix, dysregulation of polyol pathway and antioxidant enzymes, etc. In the present article, we attempted to describe a new avenue that AGE-RAGE axis culminates to different pathological consequences in brain and therefore, is a central instigating component to several neurodegenerative diseases (NGDs). We also invoke that specific inhibitors of TIR domains of TLR or RAGE receptors are crucial molecules for the therapeutic intervention of NGDs. Clinical perspectives have also been appropriately discussed.

Introduction: Postdural Puncture Headache (PDPH) is the most common complication of dural puncture. Clinical studies have shown that use of small guage needles with pencil point tip is associated with lower incidence and severity of PDPH than with cutting tip needles. Aim: To compare the incidence and severity of PDPH between 25G cutting (Quincke) and 25G non cutting (Whitacre) needles. Materials and Methods: This double-blinded, randomised controlled study was conducted at Jawaharlal Nehru Institute of Medical Sciences- Imphal, Manipur, India, from September 2019 to September 2021. A total of 150 patients of both sexes, age

The Hedge Cupid butterfly, Bothrinia chennellii (de Nicéville, 1884) (Lepidoptera: Lycaenidae) is rediscovered to Meghalaya, India, from two different localities since its last known records. The species was last recorded 63 years ago by Cantlie from Shillong, Khasi Hills, Meghalaya in 1952 and since then no records of this species has been found in the literature of the state. The species is legally protected under Schedule II of the Indian Wildlife (Protection) Act, 1972. In this paper taxonomy, distribution and current habitat of the species are discussed.

Abstract Peroxiredoxin 6 (Prdx6), the ubiquitously expressed enzyme belonging to the family of peroxidases, namely, peroxiredoxins, exhibits a unique feature of functional compartmentalization within cells. Whereas, the enzyme localized in cytosol shows glutathione peroxidase activity, its lysosomal counterpart performs calcium independent phospholipase A2 (aiPLA2) activity. Like any true moonlighting protein, these two activities of Prdx6 are mutually exclusive of each other as a function of the pH of the cellular compartments. Differential substrate preference at different pH (i.e. peroxidised phospholipids at neutral pH and reduced phospholipids at acidic pH) is considered to be the reason for this behavior. To gain insight into the pH-induced structural–functional interplay we have systematically evaluated conformational variations, thermodynamic stability of the protein and quaternary state of the conformers at both pH 7.0 and 4.0. Our findings suggest that change in pH allows alterations in native states of Prdx6 at pH 7.0 and 4.0 such that the changes make the protein resistant to thermal denaturation at low pH.

Introduction: General anaesthesia with endotracheal intubation, being one of the most commonly performed procedures in clinical anaesthesiology, is not without adverse effects. Postoperative Sore Throat (POST) is one of the common adverse effects with a varying incidence. Prophylactic management of POST is recommended to improve the quality of postanaesthesia care and recovery. Aim: To evaluate the effectiveness of preoperative nebulisation with magnesium sulphate and budesonide in reducing the incidence and severity of POST. Materials and Methods: This randomised double-blinded control study was conducted in the Department of Anaesthesiology at Jawaharlal Nehru Institute of Medical Sciences, Imphal, Manipur, India, from September 2020 to December 2021. The study included 120 patients, of either sex, aged between 20-60 years with American Society of Anesthesiologists (ASA) grade I and II posted for elective surgery requiring general anaesthesia with endotracheal intubation. The patients were randomly divided into three groups of 40 patients each. Group M was nebulised with 250 mg magnesium sulphate, Group B with 250 mcg budesonide and Group S was nebulised with normal saline, 15 minutes prior to the induction of anaesthesia. Incidence and severity of POST was documented at 0 hr, 2 hrs, 24 hrs and 48 hrs postextubation on a 0-3 score. Data collected was analysed using Statistical Package for Social Sciences (SPSS) version 22.0 and the results were then statistically analysed using Analysis of Variance (ANOVA) and Chi-square test. Results: The incidence of POST was more in saline group when compared with budesonide and magnesium sulphate group at all points of observation (0 hr, 2 hrs, 24 hrs and 48 hrs). The severity of POST was moderate in saline group while the other two groups experienced mild severity. This was statistically significant at 0 hr, 2 hrs and 24 hrs (p-value

The farmland visitor Bath White, Pontia daplidice moorei is recorded for the first time in Meghalaya. The butterfly is documented in an opportunistic survey on 17.v.2015 along the GuwahatiShillong road, near Shangbangla village at an elevation of 520 meters. This record will help in updating the status of butterfly fauna in Meghalaya, India.

Introduction: Propofol contributes largely in the rapid evolution of day care surgery due to its superior recovery characteristics. However, it is associated with dose-dependent systemic arterial hypotension which increases morbidity and mortality. Bispectral index (BIS) is an Electroencephalographic (EEG) derived parameter used to assess the depth of anaesthesia. Titrating drugs to a specific BIS value during general anaesthesia allows to adjust the dose of anaesthetic needed by the patient thereby, reducing the dose related side-effects. Aim: To determine whether the dose of propofol guided BIS values causes less arterial hypotension than the commonly used sleep dose method. Materials and Methods: The present study was a randomised control trial conducted on 92 patients of American Society of Anesthesiologists (ASA) I and II physical status, aged 18-60 years, of both genders, scheduled for elective surgeries under general anaesthesia and were randomly divided into group A and B (46 in each). For induction of anaesthesia, group A received propofol till the BIS values reached 50±1 for 30 seconds, while group B received sleep dose of propofol without BIS monitoring. Haemodynamic effects Heart Rate (HR), Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Mean Arterial Pressure (MAP) were recorded at baseline, during induction and at 1,5, 10 and 15 minutes after intubation. Total propofol consumption and secondarily, level of sedation after extubation using Ramsay Sedation Scale were also measured in both the groups. Results: The total dose requirement of propofol was reduced significantly in group A compared to group B (p0.005). On arrival to Post Anaesthesia Care Unit (PACU), group A were more co-operative, oriented patients compared to group B (67.4% vs 32.6, respectively. Conclusion: The BIS monitoring significantly reduces the consumption of propofol for induction of anaesthesia while the incidence of hypotension was similar in both the groups. Lower sedation level with comparatively better extubation score with the use of BIS helps in fast tracking.

Homocysteine (Hcy) is a sulfur containing non-protein toxic amino acid synthesized from methionine. Elevated level of Hcy is associated with cardiovascular complications and neurodegeneration. Hcy is believed to induce organ damage and apoptosis via oxidative stress. The pro-oxidant nature of Hcy is considered to originate from the metal-induced oxidation of thiol group-containing molecules forming disulfides (Hcy-Hcy, Hcy-cysteine, Hcy-glutathione, etc) or with free cysteine residues of proteins (a process called protein S-homocysteinylation). Formation of such disulfides indeed results in the generation of reactive oxygen species (ROS) which eventually leads to loss of cellular integrity. In the present manuscript, we performed systematic investigation of the effect of Hcy on iron containing proteins. We discover a novel mechanism of Hcy toxicity wherein Hcy oxidation is linked with the functional loss of the protein with iron as cofactors. Our results indicate that redox regulated heme proteins might be primarily involved in the Hcy toxicity and associated oxidative stress.