Size, site, and signaling: Three attributes of estrogen receptors Junita Desouza, Sushama Gadkar, Dhanashree Jagtap, Geetanjali Sachdeva Biomedical Research Journal 2019 6(2):37-48 Estrogens are implicated in a diverse range of functions varying from reproduction, circulation, skeletal health to neuroprotection. Estrogens are also being increasingly recognized for their pathological contribution to cancers of various organs. This has spurred several investigations on estrogen-initiated signaling mechanisms in various cell types in physiological and pathological conditions. Estrogens exert their biological actions through a class of conventional nuclear receptors known as estrogen receptors (ERs), majorly of two subtypes – ERα and ERβ, both encoded by different genes, and each has multiple isoforms. It is reported that different ER subtypes and their specific isoforms have overlapping and nonoverlapping functions. Moreover, ER functions are highly cell-context specific. Thus, it is difficult to propose a unified scheme for estrogen signaling. Another layer of complexity is added by diverse subcellular localization, i.e., nucleus, plasma membrane, and cytosol, of ERs in estrogen-responsive tissues. Size as well as site dictates the sequence of cellular events triggered by estrogen signaling. This review compiles the existing information on different subtypes, different isoforms, and different sites of subcellular localization of ERs.

Analysis of spontaneous depolarization-linked hyperpolarizations in mouse detrusor smooth muscle cells Mithun Padmakumar, Keith L Brain, Rohit Manchanda Biomedical Research Journal 2019 6(2):49-55 Background: Urinary bladder detrusor smooth muscle cells exhibit spontaneous electrical activities comprising various signal types. Aims and Objectives: This article introduces and analyzes a rare category of signals observed in such activity, named spontaneous depolarization-linked hyperpolarization (sDLH). Materials and Methods: A mouse model was used in the study, where all the occurrences of sDLHs were pooled together from multiple intracellular recording sessions. Four features – (i) resting membrane potential (RMP) (R, in mV), (ii) depolarization amplitude (D, in mV), (iii) hyperpolarization amplitude (H, in mV), and (iv) time course of the hyperpolarization (T, in ms) – were evaluated from all sDLHs. Results: The analysis of results indicated that (a) the signals appear more frequently in cells with higher RMP, (b) the depolarization amplitudes seem to be distributed randomly and have no correlation with other features, (c) hyperpolarization amplitudes show two distinct clusters and exhibit strong correlation with the RMP, and (d) time course of hyperpolarization phase shows no distinct groups and is distributed in a window larger than that of any other signals seen in the intracellular recordings. With the help of the results obtained from the analysis, a hypothesis for the biophysical origin of these signals is proposed. Conclusions: This needs to be tested experimentally, and if proved right, would help extend the boundaries of our current understanding of the detrusor smooth muscle system.

Rainfall and dengue occurrences in India during 2010–2016 Pratip Shil Biomedical Research Journal 2019 6(2):56-61 Background: A changing climate scenario coincided with the emergence and re-emergence of vectorborne diseases such as dengue, chikungunya, and Zika. The worldwide resurgence of dengue since 2005 has affected millions and generated huge disease burden, especially in the tropical developing countries including India. While India has a huge burden of dengue with all four serotypes causing outbreaks in different parts of the country, reports on climate and environmental effects on dengue are sparse. Aims and Objectives: To understand the influence of rainfall on dengue occurrences across India between 2010 and 2016, with emphasis on the most affected states. Methods: Dengue occurrence data was obtained by data mining from the NVBDCP and IDSP websites. Area-weighted-rainfall (ARF) were computed from the division-wise data. Statistical analyses performed to analyze the association between annual ARF and dengue occurrences. Spatio-temporal analyses of dengue outbreaks was conducted. Results: Spatio-temporal analyses revealed that high rainfall was positively associated with the number of cases in the northern states (Indo-gangetic Plains) whereas, the reverse was true for the southern (peninsular) states. The number of rural outbreaks of dengue had also been modulated by annual rainfall. Conclusion: Our study revealed the effect of rainfall on dengue in India. We conclude that rainfall influence the dengue occurrences differently in the northern and the southern states of India.

Protective effect of flavonoids from Foeniculum vulgare against ultraviolet-B-induced oxidative stress in human dermal fibroblasts Juilee Patwardhan, Purvi Bhatt Biomedical Research Journal 2019 6(2):62-71 Background: Traditionally, Foeniculum vulgare (fennel seeds) has been used for its antimicrobial, analgesic, antipyretic, antiflatulence, antispasmodic, and antiandrogenic activities. Materials and Methods: In the present study, the protective effect of flavonoids from fennel seeds was investigated against ultraviolet (UV)-B radiation-induced cell damage and oxidative stress in human dermal fibroblast (HDF) cells. Results: Flavonoid-enriched fraction (FEF) of fennel seeds showed high flavonoid content and antioxidant potential as well as the presence of a marker compound rutin. Pretreatment of HDF cells with the FEF (15–45 μg/ml) significantly protected against UV-B-induced cytotoxicity, endogenous enzymatic antioxidant depletion, oxidative DNA damage, intracellular reactive oxygen species generation, and apoptotic morphological changes. Conclusion: The current study proved for the first time that the FEF of fennel seeds reduced oxidative stress through the nuclear factor E2-related factor 2-antioxidant response elements pathway. Flavonoids from fennel seeds have a potential as UV-B protectants and can be explored against diseases, in which oxidative stress is closely implicated.

Therapeutic benefit of resveratrol in 5-fluorouracil-induced nephrotoxicity in rats Elias Adikwu, Innocent Biradee, Temitope Omolade Ogungbaike Biomedical Research Journal 2019 6(2):72-77 Background: The prevention of nephrotoxicity caused by 5-fluorouracil (5-FU) can improve patients' adherence to treatment.Aim and Objective: This study assessed the ability of resveratrol (RES) to prevent 5-FU-induced nephrotoxicity in rats. Materials and Methods: Forty adult male albino rats randomized into eight groups of n = 5 were used. Group A (control) was administered with 0.2 mL of normal saline intraperitoneally (i.p.), whereas Groups B-D were administered with 10, 20, and 40 mg/kg of RES daily for 5 days respectively. Group E was administered with 20 mg/kg of 5-FU ip daily for 5 days. Groups F-H were administered with 10 mg/kg of RES + 20 mg/kg of 5-FU, 20 mg/kg of RES + 20 mg/kg of 5-FU, and 40 mg/kg of RES + 20 mg/kg of 5-FU ip daily for 5 days, respectively. Blood samples were collected after rats were sacrificed and evaluated for serum renal function biomarkers. Kidneys were evaluated for oxidative stress markers and histology. Results: Serum creatinine, urea, and uric acid levels were significantly (P < 0.001) increased, whereas total protein, albumin, potassium, sodium, chloride, and bicarbonate levels were significantly (P < 0.001) decreased in 5-FU-treated rats when compared to control. Kidney superoxide dismutase, glutathione, glutathione peroxidase, and catalase levels were significantly (P < 0.001) decreased, whereas malondialdehyde levels were significantly increased in 5-FU-treated rats when compared to control. Furthermore, the kidneys of 5-FU-treated rats showed tubular necroses and atrophic glomeruli. The aforementioned nephrotoxic changes were significantly abrogated in rats supplemented with 10 mg/kg (P < 0.05), 20 mg/kg (P < 0.01), and 40 mg/kg (P < 0.001) of RES when compared to 5-FU. Conclusion: RES may have therapeutic benefit in nephrotoxicity caused by 5-FU.

Transplantation review: Liver, kidney, and pancreas transplantation Rakesh Rai Biomedical Research Journal 2019 6(2):78-81