The effect of exposure to RF-EMF from the laboratory simulator of 5G NR base station on physiological parameters and cognitive abilities of male wistar rats of different ages.

In this article, the impact of radiofrequency electromagnetic field (RF-EMF) exposure from a simulated base station for the 5G New Radio (5G NR) telecommunication on rats was studied. The base station affects all age groups of the population, thus, for the first time, the experiment was conducted on male Wistar rats of three different ages (juvenile, adult, and presenile). The base station exposure parameters were chosen according to ICNIRP recommendations for limiting the exposure to radiofrequency electromagnetic field: frequency 2.4 GHz with an average specific absorption rate of 0.0076 W/kg and 0.0059 W/kg over the whole body of experimental animals. Throughout the experiment, body weight was examined weekly, and the dynamics of body weight gain was monitored. Rectal and skin surface temperature on the right hind limb was monitored weekly. Testing in the Morris water maze was performed during the last, Week 5, of RF-EMF exposure. After euthanasia, organ weights were determined in experimental and control animals. None of the investigated parameters did show any statistically significant differences between exposed and control animals of the same age. The data obtained can be used to assess the possible consequences of chronic exposure to RF-EMF from 5G NR base stations.

Cyclooxygenase-2 (COX-2) Expression in Oral Submucous Fibrosis and Oral Squamous Cell Carcinoma: An Immunohistochemical Study.

Introduction: Growing evidence has shown that cyclooxygenase-2 (COX-2), an enzyme capable of catalyzing prostaglandin production, plays a key role in carcinogenesis. Selective COX-2 inhibitors have been shown to reduce the establishment of tumors such as oral squamous cell carcinoma (OSCC) and premalignant conditions such oral submucous fibrosis (OSMF) in experimental models. The aim of this study was to investigate the immunohistochemical expression of COX-2 in OSCC and OSMF with the normal oral mucosa as control. Material and Methods: Forty-five formalin-fixed paraffin-embedded samples comprising 20 OSCC, 20 OSMF, and 5 normal oral mucosa specimens were withdrawn from the archives of the Department of Oral and Maxillofacial Pathology for immunohistochemical examination for COX-2 expression. Negative and less than 5% COX-2 positivity was considered negative expressions, while greater than or equal to 5% COX-2 positivity was considered positive expression. The data obtained were statistically analyzed. Results: The difference in percentages of expression in normal mucosa, OSCC, and OSMF was highly significant (P < 0.01). In comparison to normal mucosa, OSCC and OSMF had an increased level of COX-2 expression. However, there was an insignificant difference between the various histological gradings of OSCC and OSMF. Conclusion: The results of the present study confirm the role of COX-2 in carcinogenesis and in the progression of premalignant conditions to malignancy.

Effectiveness of molecular-targeted chemotherapy in ameloblastomas: A systematic review.

Ameloblastoma is a benign, locally aggressive neoplasm that needs extensive surgical resection. The goal of this article is to obtain an in-depth review of benign ameloblastomas to determine the available level of evidence and the possible benefit of targeted therapeutics for the treatment of ameloblastoma and BRAF V600E mutation in ameloblastoma. An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE, EBSCO, and Web of Science for eligible studies published between 1975 and 2021. The systematic review is registered with INPLASY (INPLASY202260018). The review included 2 case series and 17 case reports. The histopathological type, anatomic location, expression of BRAF mutation, additional mutations, and molecular-targeted therapies of the 19 reviewed articles were summarized and tabulated. Interestingly, the majority of the primary site of ameloblastoma was located in the mandible (80.9%) compared to the maxilla (17%). The tumour size was reported in nine of the included studies. Most of the included studies in the review exhibited ameloblastoma with BRAF V600E mutations and responded to molecular-targeted therapies. Molecular therapies employing BRAF and/or MEK inhibitors in ameloblastoma with BRAF V600E mutations proved to be an appropriate treatment based on the limited available evidence. It is essential further to deepen our understanding at the clinical and molecular level to enhance the precision of management of ameloblastoma.

Possible role of miR-2909 RNomics in arsenic mediated pancreatic ß-cell dysfunction.

Chronic exposure of humans to inorganic arsenic as a potential risk for the incidence of diabetes has received wide attention. However, the biological mechanism through which arsenic plays a role in the development of diabetes is still being evaluated. One of the hallmark of diabetes is the ß-cell dysfunction followed by the changes in the insulin secretion. Pancreatic duodenal homeobox 1 (PDX1) has been widely recognized to play crucial role in the ß-cell development, survival and its regulation of insulin gene expression. Many of the arsenic mediated cellular affects have been shown to be regulated by miR-2909 in vitro. Our present study provides evidence to reveal that arsenic affects miR-2909 expression in the pancreatic ß-cell and this novel miRNA regulates PDX1 transcriptional expression indirectly through genes coding for c-Jun, MafA, PI3K and directly at the translational level by targeting the PDX1 mRNA. We provide further evidence for this miR-2909 RNomics in pancreatic tissue obtained from NOD mice where the expression of miR-2909 was high compared to the control mice. Keeping in view the fact that arsenic is known to cause ß-cell dysfunction and most of the cellular effects of arsenic have been shown to be mediated through miR-2909 RNomics, our study revealed that arsenic employs miR-2909 (at low doses) and c-Jun (at high doses) to down regulate PDX1 in order to cause ß-cell dysfunction leading to diabetic state.

AHNAK KO mice are protected from diet-induced obesity but are glucose intolerant.

AHNAK is a 700 KD phosphoprotein primarily involved in calcium signaling in various cell types and regulating cytoskeletal organization and cell membrane architecture. AHNAK expression has also been associated with obesity. To investigate the role of AHNAK in regulating metabolic homeostasis, we studied whole body AHNAK knockout mice (KO) on either regular chow or high-fat diet (HFD). KO mice had a leaner phenotype and were resistant to high-fat diet-induced obesity (DIO), as reflected by a reduction in adipose tissue mass in conjunction with higher lean mass compared to wild-type controls (WT). However, KO mice exhibited higher fasting glucose levels, impaired glucose tolerance, and diminished serum insulin levels on either diet. Concomitantly, KO mice on HFD displayed defects in insulin signaling, as evident from reduced Akt phosphorylation and decreased cellular glucose transporter (Glut4) levels. Glucose intolerance and insulin resistance were also associated with changes in expression of genes regulating fat, glucose, and energy metabolism in adipose tissue and liver. Taken together, these data demonstrate that (a) AHNAK is involved in glucose homeostasis and weight balance (b) under normal feeding KO mice are insulin sensitive yet insulin deficient; and (c) AHNAK deletion protects against HFD-induced obesity, but not against HFD-induced insulin resistance and glucose intolerance in vivo.

CYP2E1 impairs GLUT4 gene expression and function: NRF2 as a possible mediator.

Impaired GLUT4 function/expression in insulin target tissues is well-documented in diabetes and obesity. Cytochrome P450 isoform 2E1 (CYP2E1) induces oxidative stress, leading to impaired insulin action. CYP2E1 knockout mice are protected against high fat diet-induced insulin resistance and obesity; however the molecular mechanisms are still unclear. We examined whether CYP2E1 impairs GLUT4 gene expression and function in adipose and muscle cells. CYP2E1 overexpression in skeletal muscle-derived L6 cells inhibited insulin-stimulated Glut4 translocation and 2-deoxyglucose uptake, with the latter inhibition being blocked by vitamin E. CYP2E1 overexpression in L6 and primary rat adipose (PRA) cells suppressed GLUT4 gene expression at promoter and mRNA levels, whereas CYP2E1 silencing had opposite effects. In PRA, CYP2E1-induced suppression of GLUT4 expression was blocked by chlormethiazole (CYP2E1-specific inhibitor) and the antioxidants vitamin E and N-acetyl-l-cysteine. CYP2E1 effect was mediated by the transcription factor NF-E2-related factor 2 (NRF2), as evident from its complete reversal by a coexpressed dominant-negative, but not wild-type NRF2. GLUT4 transcription was suppressed by NRF2 overexpression, and enhanced by NRF2 silencing. Promoter and ChIP analysis showed a direct and specific binding of NRF2 to a 58-326 GLUT4 promoter region that was required to maintain CYP2E1 suppression; this binding was enhanced by CYP2E1 overexpression. We suggest a mechanism for CYP2E1 action that involves: a) suppression of GLUT4 gene expression that is mediated by NRF2; b) impairment of insulin-stimulated Glut4 translocation and function. CYP2E1 and NRF2 are introduced as negative regulators of GLUT4 expression and function in insulin-sensitive cells.

Diagnostic and prognostic utility of rapid strip (OptiMal and Paracheck) versus conventional smear microscopy in adult patients of acute, uncomplicated P. falciparum malaria in Mumbai, India.

OBJECTIVES: The present study compared the diagnostic and prognostic utility of two rapid tests the (Paracheck and OptiMal) versus conventional smear microscopy. METHODS: Using two independent microscopists we carried out the three tests in 31 adult cases of smear positive, acute, uncomplicated Plasmodium falciparum malaria. All three tests were done pretreatment, and on Days 8, 15 and 29. RESULTS: Compared to microscopy, the Paracheck had a sensitivity of 100%, while the OptiMal had a sensitivity of 83.7%. The lower sensitivity of OptiMal resulted from misidentification by both microscopists of 6/31 cases as Plasmodium vivax. As a follow up tool, the OptiMal was better than Paracheck, due to the earlier disappearance of the parasite LDH. Also in the Paracheck, between microscopists, there was a significant difference in reading the tests, on Days 8 and 15. CONCLUSION: Our study reiterates, the continued utility of conventional smear microscopy.

Alginate encapsulated bioadhesive chitosan microspheres for intestinal drug delivery.

Sustained intestinal delivery of drugs such as 5-fluorouracil (choice for colon carcinomas) and insulin (for diabetes mellitus) seems to be a feasible alternative to injection therapy. For successful therapy, the drug should be delivered at proper sites (here, the intestine) for long duration, for producing maximum pharmacological activity. We have attempted to develop a formulation that can bypass the acidity of the stomach and release the loaded drug for long periods into the intestine by using the bioadhesiveness of polyacrylic acid, alginate, and chitosan. Bromothymol blue was taken as a model drug. The formulation exhibited bioadhesive property and released the drug for an eight-day period in vitro.