Residues of TRPM8 at the Lipid-Water-Interface have Coevolved with Cholesterol Interaction and are Relevant for Diverse Health Disorders.

TRPM8 is a non-selective cation channel that is expressed in several tissues and cells and also has a unique property to be activated by low-temperature. In this work, we have analyzed the conservation of amino acids that are present in the lipid-water-interface (LWI) region of TRPM8, the region which experiences a microenvironment near the membrane surface. We demonstrate that the amino acids present in the LWI region are more conserved than the transmembrane or even full-length TRPM8, suggesting strong selection pressure in these residues. TRPM8 also has several conserved cholesterol-binding motifs where cholesterol can bind in different modes and energies. We suggest that mutations and/or physiological conditions can potentially alter these TRPM8-cholesterol complexes and can lead to physiological disorders or even apparently irreversible diseases such as cancer and neurodegeneration.

ELONGATED HYPOCOTYL 5 (HY5) and POPEYE (PYE) regulate intercellular iron transport in plants.

Plants maintain iron (Fe) homeostasis under varying environmental conditions by balancing processes such as Fe uptake, transport and storage. In Arabidopsis, POPEYE (PYE), a basic helix-loop-helix transcription factor (TF), has been shown to play a crucial role in regulating this balance. In recent years, the mechanisms regulating Fe uptake have been well established but the upstream transcriptional regulators of Fe transport and storage are still poorly understood. In this study, we report that ELONGATED HYPOCOTYL5 (HY5), a basic leucine zipper (bZIP) TF which has recently been shown to play a crucial role in Fe homeostasis, interacts with PYE. Molecular, genetic and biochemical approaches revealed that PYE and HY5 have overlapping as well as some distinct roles in the regulation of Fe deficiency response. We found that HY5 and PYE both act as a repressor of Fe transport genes such as YSL3, FRD3, NPF5.9, YSL2, NAS4 and OPT3. HY5 was found to directly bind on the promoter of these genes and regulate intercellular Fe transport. Further analysis revealed that HY5 and PYE directly interact at the same region on PYE and NAS4 promoter. Overall, this study revealed that HY5 regulates Fe homeostasis by physically interacting with PYE as well as independently.

SOD-GIF-FIT module controls plant organ size and iron uptake.

Plant organ growth is controlled by various internal and external cues. However, the underlying molecular mechanisms that coordinate plant organ growth and nutrient homeostasis remain largely unknown. Recently, Zheng et al. identified the key regulators SOD7 (suppressor of da1-1) and GRF-INTERACTING FACTOR1 (GIF1) that control organ size and iron uptake in arabidopsis (Arabidopsis thaliana).

Risk factors of osteoporosis in soldiers of the Armed Forces: A cross-sectional study from Western India.

Background: Osteoporosis may result from risk factors such as smoking, alcohol, low body mass index, less physical exercise, and dietary calcium deficiency. The risk of osteoporosis fractures can be reduced with lifestyle changes, which include diet, exercise, and preventing falls. The present study is an effort to measure the burden of risk factors of osteoporosis in adult male soldiers in the Armed Forces. Methods: The present study was a cross-sectional study among serving soldiers in South-Western part of India, and 400 participants consented to be included in the study. After obtaining informed consent, the questionnaire was distributed. Venous blood samples were collected to measure serum calcium, phosphorus, vitamin D, and parathyroid hormone (PTH). Results: The prevalence of vitamin D3 severe deficiency (<10 ng/mL) was 38.5%, and the prevalence of vitamin D3 deficiency (10-19 ng/mL) was 33%. Low serum calcium (<8.4 mg/dL) and serum phosphorus (<2.5 mg/dL) were found among 19.5% and 11.5%, respectively, whereas a raised serum PTH level (>66.5 pg/mL) was seen in 5.5% of the participants. A statistically significant association was found between consumption of milk and milk products and levels of calcium. With a cutoff value of 20 ng/mL for vitamin D3 deficiency, a statistically significant association was found for consumption of fish, physical activity, and sun exposure. Conclusion: A remarkably large percentage of otherwise normal healthy soldiers have deficiency or insufficiency of vitamin D and might be prone to osteoporosis. Despite significant advances in our understanding and management options for male osteoporosis, there still remain important gaps in knowledge which needs to be looked into.

Evaluation of potential toxic heavy metal contamination in soil, fly ash, vegetables and grain crops along with associated ecological and health risk assessment of nearby inhabitants of a thermal power station in Jharkhand (India).

The present study aimed to evaluate the potential toxic heavy metal (PTHM) concentrations and associated ecological and health risk of nearby inhabitants (child and adult populations) of the Bokaro thermal power station (BTPS), Jharkhand, India. The fly ash containing PTHMs is released from the thermal power plant and contaminates the soil of the nearby agricultural area, roadside area and residential area. Furthermore, PTHMs cause ecological risk as well as carcinogenic health effects in adults. Inhabitants are exposed to PTHMs through exposure pathways (for instance, direct ingestion, dermal contact and air inhalation), and PTHMs were examined in this study by calculating the estimated daily intake (EDI). The contamination factor (Cf) of Cd exceeded the threshold value throughout the study area, whereas the Cf of Hg was observed higher only in roadside soil (RSS). The geoaccumulation index (Igeo) of Cd was higher in the top soil of agricultural soil (AS) (7.39) and RSS (9.38). The level of PTHMs was monitored slightly higher in the topsoil of RSS. The ecological risk index (Eri) was detected to be the highest in RSS (1628.9). The permissible limit of Cd (0.05 mg kg-1) and Pb (0.1 mg kg-1) for all sampled vegetables and grain crops was surpassed. The transfer factor (TF) of the studied vegetables and grain crops was in the order of Cd > Cr > Pb > Hg > As. The results of the present study concluded that the hazard quotient (HQ) values for all PTHMs analysed in soil throughout the study area were < 1, which indicates that the child population was within the safe limit. However, the adult population was at a high risk of non-carcinogenic health effects due to increased permissible limits of Cd, Pb and Cr in vegetables and grain crops whereas the target carcinogenic risk (TCR) of Pb and Cr was higher and indicated that there may be a health risk of cancer in adults.

Functionality of apigenin as a potent antioxidant with emphasis on bioavailability, metabolism, action mechanism and in vitro and in vivo studies: A review.

Numerous diseases such as cancer, diabetes, cardiovascular, neurodegenerative diseases, etc. are linked with overproduction of reactive oxygen species (ROS) and oxidative stress. Apigenin (5,7,4'-trihydroxyflavone) is a widely distributed flavonoid, responsible for antioxidant potential and chelating redox active metals. Being present as glycosides or polymers, the apigenin degrades to variable amount in the digestive tract; during processing, its activity is also reduced due to high temperature or Fe/Cu addition. Although its metabolism remains elusive, enteric absorption occurs sufficiently to reduce plasma indices of oxidant status. Delayed clearance in plasma and slow liver decomposition enhance its systematic bioavailability. Antioxidant mechanism of apigenin includes: oxidant enzymes inhibition, modulation of redox signaling pathways (NF-kB, Nrf2, MAPK, and P13/Akt), reinforcing enzymatic and nonenzymatic antioxidant, metal chelation, and free radical scavenging. DPPH, ORAC, ABTS, and FRAP are the major in vitro methods for determining the antioxidant potential of apigenin, whereas its protective effects in whole and living cells of animals are examined using in vivo studies. Due to limited information on antioxidant potential of apigenin, its in vitro and in vivo antioxidant effects are, therefore, discussed with action mechanism and interaction with the signaling pathways. This paper concludes that apigenin is a potent antioxidant compound to overcome the difficulties related to oxidative stress and other chronic diseases.

An Energy-Resolved Optical Non-invasive Device Detects Essential Electrolyte Balance in Humans at Point-of-Care.

Regular monitoring of electrolyte balance is essential for patients suffering from chronic kidney disease (CKD), particularly those undergoing dialysis. In the context of the recent COVID-19 pandemic, more severe forms of infection are observed in elderly individuals and patients having co-morbidities like CKD. The repeated blood tests for the monitoring of electrolyte balance predispose them not only to COVID-19 but also other to hospital-acquired infections (HAI). Therefore, a non-invasive method for easy detection of essential electrolyte (K+ and Na+) levels is urgently needed. In this study, we developed an optical emission spectroscopy-based non-invasive device for simultaneous monitoring of salivary Na+ and K+ levels in a fast and reliable way. The device consisted of a closed spark chamber, micro-spectrometer, high voltage spark generator, electronic circuits, optical fiber, and an indigenously developed software based on the LabVIEW platform. The optical emission originating from the biological sample (i.e., saliva) due to recombination of ions energized by impingement of electrons returning from high voltage spark provides necessary information about the concentration of electrolytes. A small-scale clinical trial on 30 healthy human subjects shows the potential of the indigenously developed device in determining salivary Na + and K+ concentration. The low-cost, portable, point-of-care device requires only 2 mL of sample, and can simultaneously measure 1.0-190.0 mM Na+, and 1.0-270.9 mM K+ . To our understanding, the present work will find its relevance in combating COVID-19 morbidities, along with regular CKD patient-care.

Spectroscopic Studies on the Biomolecular Recognition of Toluidine Blue: Key Information Towards Development of a Non-Contact, Non-Invasive Device for Oral Cancer Detection.

Molecular interaction of aromatic dyes with biological macromolecules are important for the development of minimally invasive disease diagnostic biotechnologies. In the present work, we have used Toluidine Blue (TB) as a model dye, which is a well-known staining agent for the diagnosis of oral cancer and have studied the interaction of various biological macromolecules (protein and DNA) with the dye at different pH. Our spectroscopic studies confirm that TB interacts with Human Serum Albumin (HSA), a model protein at very high pH conditions which is very hard to achieve physiologically. On the other hand, TB significantly interacts with the DNA at physiological pH value (7.4). Our molecular studies strengthen the understanding of the Toluidine Blue staining of cancer cells, where the relative ratio of the nucleic acids is higher than the normal intracellular content. We have also developed a non-invasive, non-contact spectroscopic technique to explore the possibility of quantitatively detecting oral cancer by exploiting the interaction of TB with DNA. We have also reported development of a prototype named "Oral-O-Scope" for the detection of Oral cancer and have carried out human studies using the prototype.

Generalized Anxiety disorder but not depression is associated with insomnia: a population based study.

BACKGROUND: Insomnia is a common problem, however, its prevalence has never been examined in Indian population. Moreover, a number of psychiatric disorders have been found to be associated with insomnia in clinical population, but this association has scarcely been examined in general population. METHODS: This epidemiological study was done in an urban and a rural population. Subjects were selected using Kish method. After obtaining informed consent, psychiatric disorders were diagnosed using Hindi version of Mini International Neuropsychiatric Interview. Hindi version of Insomnia Severity Index was used to diagnose insomnia. RESULTS: 1700 subjects were included in this study. In this study, prevalence of insomnia was 10.3%. Its prevalence increased with increasing years of education (p=0.009). Insomnia was more frequent in subjects living in joint families (p<0.001), having higher education (p=0.009), those who were separated (p<0.001), among subjects belonging to middle socio-economic status (p<0.001) and in urban population compared to semi-urban and rural population (p<0.001). Insomnia was also more frequent among subjects with major depressive disorder, generalized anxiety disorder, alcohol dependence, cannabis dependence and tobacco use. However, binary logistic regression analysis showed that only higher education, unemployment, generalized anxiety disorder and tobacco use were associated with insomnia. CONCLUSION: Insomnia in general population is associated with higher education, unemployment, generalized anxiety disorders and tobacco use.

Ileal Neobladder With Mucous Plugs as a Cause of Obstructive Acute Kidney Injury Requiring Emergent Hemodialysis.

Ileal neobladder is the preferred technique in the management of urinary diversion postradical cystectomy for bladder malignancy. The common complications associated with this procedure are atrophied kidney, chronic pyelonephritis, decreased renal function, ureteroileal or urethral anastomotic site stricture, urinary tract stones, incontinence, and hyperchloremic metabolic acidosis. Mucous plugs are also seen in 2%-3% patients. We present a rare presentation of a patient who required hemodialysis for severe hyperkalemia and acute kidney injury caused by mucous plugging of ileal neobladder.