Different mechanisms of arsenic related signaling in cellular proliferation, apoptosis and neo-plastic transformation.

Arsenic is a toxic heavy metal vastly dispersed all over the earth crust. It manifests several major adverse health issues to millions of arsenic exposed populations. Arsenic is associated with different types of cancer, cardiovascular disorders, diabetes, hypertension and many other diseases. On the contrary, arsenic (arsenic trioxide, As2O3) is used as a chemotherapeutic agent in the treatment of acute promyelocytic leukemia. Balance between arsenic induced cellular proliferations and apoptosis finally decide the outcome of its transformation rate. Arsenic propagates signals via cellular and nuclear pathways depending upon the chemical nature, and metabolic-fates of the arsenical compounds. Arsenic toxicity is propagated via ROS induced stress to DNA-repair mechanism and mitochondrial stability in the cell. ROS induced alteration in p53 regulation and some mitogen/ oncogenic functions determine the transformation outcome influencing cyclin-cdk complexes. Growth factor regulator proteins such as c-Jun, c-fos and c-myc are influenced by chronic arsenic exposure. In this review we have delineated arsenic induced ROS regulations of epidermal growth factor receptor (EGFR), NF-ĸß, MAP kinase, matrix-metalloproteinases (MMPs). The role of these signaling molecules has been discussed in relation to cellular apoptosis, cellular proliferation and neoplastic transformation. The arsenic stimulated pathways which help in proliferation and neoplastic transformation ultimately resulted in cancer manifestation whereas apoptotic pathways inhibited carcinogenesis. Therapeutic strategies against arsenic should be designed taking into account all these factors.

ACE/ACE2 balance might be instrumental to explain the certain comorbidities leading to severe COVID-19 cases.

The outbreak of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a global catastrophe. The elderly and people with comorbidity are facing a serious complication of the disease. The entry and infection strategy of SARS-CoV-2 in a host cell is raised by an amazing way of angiotensin-converting enzyme (ACE) 2 (ACE2) receptor recognition and imbalance of ACE/ACE2 in various organs, especially in the lungs. Here it has been discussed the role of interferon and protease during the receptor recognition (begining of infection) and followed by the impact of cytokine and hypoxia in the context of the balance of ACE/ACE2. It has also very concisely delineated the biochemistry and mechanism of ACE/ACE2 balance in different stages of infection and its role in comorbidity.

Functional Role of the Rodlet Cell and Macrophage in Neural Protection of the Olfactory Neuroepithelium in a Teleostean: Gobiid (Pseudapocryptes lanceolatus [Bloch and Schneider, 1801]): An Ultrastructural Study.

BACKGROUND: Neural protection of the olfactory epithelium against pathogenic invasion is still hardly addressed in fish chemosensory research. AIMS AND OBJECTIVES: The ultrastructural detail on the rodlet cell and macrophage has been studied within the olfactory neuroepithelium of Pseudapocryptes lanceolatus to correlate their role in the neural protection of the chemosensory system. MATERIALS AND METHODS: The cellular structures were examined under light microscope (LM: Primo Star; Carl Zeiss Microscopy, GmbH, Germany) and transmission electron microscope (Morgagni 268D). RESULTS: Three distinct stages of the rodlet cell (viz., immature, mature, and degenerative) and macrophages have been characterized at the various depths of the olfactory neuroepithelium in P. lanceolatus. The cytoarchitecture of degenerative rodlet cell indicates holocrine mode of secretion against pathogenic invasion into the nasal cavity. Macrophages possess prominent pseudopodia, extending toward invading pathogens. The interaction between macrophage and invading pathogens implicates the role of macrophage as a scavenger to eliminate the pathogens by phagocytosis from the neuroepithelial system. CONCLUSION: This study denotes a significant difference in the mode of action of rodlet cell and macrophages, but they are commonly involved in cell-mediated nonspecific immune response against the invading pathogens.

Ultrastructure Based Morphofunctional Variation of Olfactory Crypt Neuron in a Monomorphic Protogynous Hermaphrodite Mudskipper (Gobiidae: Oxudercinae) (Pseudapocryptes lanceolatus [Bloch and Schneider]).

Pseudapocryptes lanceolatus (Bloch and Schneider) is a monomorphic protogynous hermaphrodite teleost that possesses ovotestis as gonadal unit of reproductive structure. At the onset of breeding season (i.e., June-July), the ovarian tissue is gradually differentiating into female-phased P. lanceolatus. At the same time, the pear-shaped crypt cells (a type of neuron) are frequently appeared at apical part of pseudostratified olfactory neuroepithelium of P. lanceolatus. The crypt neuron is characterized by the presence of sunken cilia and microvilli at the proximal region. The features of subcellular organelles are also explored in lieu of their probable functional significance. The nucleoplasm of mature crypt neuron shows chromatin granules having diameter: 15-25 nm. This cell undergoes neural apoptosis at the end of breeding phase (i.e., October-November). Fragmented chromatin fibers with numerous chromatin granules (diameter: 25-30 nm) in nucleoplasm and lysosomal diversity are the most notable characters of apoptotic crypt neuron. The large accumulation of heterochromatin chromatins in nucleoplasm is also marked under fluorescence microscope. The frequent presence of acetylcholinesterase-positive vesicles in axoplasm of crypt neurons is also a prime subcellular indicator for inhibition of neural transmission of olfactory signals. Therefore, it is concluded that the sex differentiation in P. lanceolatus and occurrence of crypt neuron in olfactory neuroepithelium are interrelated events during the reproductive period. Consequently, we hypothesized that the crypt neuron plays an active role in the implementation of unique reproductive strategy through recognition of pheromonal cues within the social organization of P. lanceolatus.

Attenuation of utero-toxicity, metabolic dysfunction and inflammation by soy protein concentrate in rats exposed to fluoridated water: consequence of hyperlipidemia in parallel with hypohomocysteinemia.

Lipid peroxidation and ROS generation are the pathogenesis of chronic fluoride toxicity, and its detrimental effects on human reproduction are noted drastically. The aim of the present study was to elucidate the defensive effects of soy protein concentrate (SPC) against sodium fluoride (NaF)-induced uterine dysfunction at biochemical and histological level. Rats were randomly distributed into four groups as control, NaF-treated (200 ppm), and SPC co-administered groups (20 mg and 40 mg/ 100 g body weight) for 16 days. SPC reversed the toxic effects of NaF. SPC significantly ameliorated the NaF-induced alterations of the antioxidant system in the uterus by decreasing lipid peroxidation products and by increasing antioxidant activities. SPC significantly counteracted the adverse effects of NaF on serum level of lactate dehydrogenase (LDH) and inflammatory markers Interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and nuclear factor kappa-B (NF-κB). Our results also explored that lipid profile was meaningfully altered due to NaF and also focused a diminution of circulating homocysteine (Hcy) and altered lipid profiles along with a diminished quantity of serum B12 and B9. However, both the doses of SPC reverted back serum levels of B12, B9, and Hcy status in similar fashion along with its corrective action on lipid profile. NaF-treated group exhibited a marked degree of reduction in the weights of ovary and uterus with an alteration of normal tissue histology and significant diminution in serum estradiol (ES) levels without fluctuating uterine estradiol receptor-α (ER-α). However, SPC restored the normal tissue histoarchitecture and also increased the functional efficiency and expression of the ER-α receptor by overturning the ES levels in NaF-treated rats. Moreover, both the doses of SPC were effective against NaF-induced alterations, although 40 mg SPC/100 g body weight had better efficacy in ameliorating the NaF-induced adverse effects on the uterus and ovary.

Estriol Inhibits Dermcidin Isoform-2 Induced Inflammatory Cytokine Expression Via Nitric Oxide Synthesis in Human Neutrophil.

BACKGROUND: An increase in the level of cytokines like TNF-α and IL-6 causes the inflammatory surge in acute ischemic heart disease (AIHD). OBJECTIVE: A high-level dermcidin isoform-2 (DCN-2) occurrence in AIHD was subjected to determine a possible regulation of cytokines expression. The effect of estrogen to counteract the inflammatory response was determined. METHODS: Blood was collected from AIHD patients and normal volunteers with consent. Nitric oxide (NO) synthesis was done with methemoglobin method.TNF-α and IL-6 expression were determined by ELISA and Western blot. RESULTS: (DCN-2) incubation with 120nM to the normal neutrophil solution for 2h resulted in the increase of TNF-α from 3.82±1.53pg/ml to 20.7±6.9pg/ml and IL-6 from 3.27±1.52pg/ml to 47.07±3.4pg/ml. In AIHD patients, the cytokine level was18.3- 27.3pg/ml, with a median value 21.86pg/ml (TNF-α) and IL-6 level was 23.54- 52.73pg/ml, with a median value 42.16pg/ml. Treatment with 0.6nM estriol, a kind of female steroid hormone estrogen for 45min decreased the elevated cytokine level in 120nM DCN-2 treated normal neutrophils. DCN-2 induced TNF-α synthesis in neutrophils was further determined by Western blot technique with a thickened band intensity of TNF-α. Estriol (0.6nM) treatment also influenced the DCN-2 induced inhibition of nitric oxide (NO) synthesis from 0nmol NO/ml to 0.56nmol/ml. The subsequent reduction of TNF-α level correlates the increase of NO level. CONCLUSION: In conclusion, the stress-induced DCN-2 production in AIHD propagates the inflammatory response. Steroid molecule like estriol plays a protective role by reducing DCN-2 responses in the NO synthesis.