A community-based study of dental fluorosis in rural children (6-12 years) from an aspirational district in Karnataka, India.

Objectives: The present study was planned to estimate the prevalence of dental fluorosis in 6-12 years of children and its association with various drinking water sources, water, and urine fluoride levels among the subset of children under the umbrella of a larger study to address iodine deficiency disorders and iron deficiency anemia in 17 villages of Manvi and Devadurga talukas of Raichur district of Karnataka. Methods: Analysis of subset of data and urine samples of children under the umbrella of a larger cross-sectional community-based study was conducted in 17 villages of Manvi and Devadurga taluks of Raichur district. House to house survey was carried out to collect data using a semi-structured questionnaire in ODK software. Demographic details, source of drinking water, clinical assessment of dental fluorosis, and height and weight measurements were performed by trained staff. Urine and water samples were collected for fluoride level estimation. The overall prevalence of dental fluorosis and its severity-wise prevalence were estimated. Association between dental fluorosis and age, gender, type of diet, source of drinking water, height for age, BMI for age, water fluoride level, and urine fluoride level were carried out using logistic regression analysis. Results: The prevalence of dental fluorosis was 46.0%. Mild, moderate, and severe dental fluorosis was found in 37.9, 7.8, and 0.3% of children. With the increasing age of participants, the odds of dental fluorosis were found to increase by 2-4 folds. The odds of having dental fluorosis were significantly increased with increasing water fluoride levels of 3 to 5 ppm [AOR = 3.147 (1.585-6.248); P = 0.001] in comparison with water fluoride levels of < 1 ppm. The similar trend was found with urine fluoride level > 4 ppm [AOR = 3.607 (1.861-6.990); P < 0.001]. As compared to river water, other sources of drinking water were significantly associated with higher odds of dental fluorosis. Conclusions: Prevalence of dental fluorosis was high in 6 to 12 years due to overexposure of fluoride from drinking water. High water and urine fluoride levels in children indicate the chronic exposure to fluoride and suggest that the population is at high risk of developing chronic fluorosis.

Mitophagy in Carcinogenesis and Tumour Progression- A New Paradigm with Emerging Importance.

The term Mitophagy has been newly concerned in reforming the metabolic landscape inside cancerous cells in addition to the interface between malignant cells as well as other major constituents of tumour microenvironment. Several profoundly interrelated systems, comprising mitochondrial dynamics and mitophagy, function in mammalian cells as vital mitochondrial regulator processes, and their consequence in neoplastic development has recently been illuminated clinically. In specific instances of cancer cells, mitochondrial-protected metabolic paths are revamped to meet expanded bioenergetics along with biosynthetic necessities of malignant cells, in addition to deal with oxidative stress. It is an exhausting task to foresee the role that mitophagy has on malignant growth cells since it relies upon various elements like cancer variability, malignant growth phase, genetic background and harmony between cell demand and accessibility. As per condition, mitophagy may have a double role as cancer suppressor for example Atg5 (autophagy related 5) or Atg7 (autophagy related 7) or execute promoter like function for instance FUNDC1 (FUN14 domain-containing protein 1), BNIP3 (BCL2/adenovirus E1B 19-kDa-interacting protein 3), PINK1 (PTEN-instigated kinase 1) etc. Tumour suppressive function of Parkin (E3 ubiquitin ligase) is likewise distinguished in mammary gland carcinoma where obstruction of mitophagy impacts tumour progression. In pancreatic cancer cells and hepatocellular carcinoma hypermethylation of the BNIP3, promoter occurs that prevent HIF-1 (Hypoxia-Inducible Factor 1) binding besides ensuing initiation of mitophagy. Since the dual role of mitophagy has in malignant growth relying upon various circumstances and cell varieties, a range of studies have been performed on mitophagy and its role in cancer progression and development is opening up a new paradigm with immense clinical importance.

Cancer Immunology and CAR-T Cells: A Turning Point Therapeutic Approach in Colorectal Carcinoma with Clinical Insight.

Cancer immunotherapy endeavours in harnessing the delicate strength and specificity of the immune system for therapy of different malignancies, including colorectal carcinoma. The recent challenge for cancer immunotherapy is to practice and develop molecular immunology tools to create tactics that efficiently and securely boost antitumor reactions. After several attempts of deceptive outcomes, the wave has lastly altered and immunotherapy has become a clinically confirmed treatment for several cancers. Immunotherapeutic methods include the administration of antibodies or modified proteins that either block cellular activity or co-stimulate cells through immune control pathways, cancer vaccines, oncolytic bacteria, ex vivo activated adoptive transfer of T cells and natural killer cells. Engineered T cells are used to produce a chimeric antigen receptor (CAR) to treat different malignancies, including colorectal carcinoma in a recent decade. Despite the considerable early clinical success, CAR-T therapies are associated with some side effects and sometimes display minimal efficacy. It gives special emphasis on the latest clinical evidence with CAR-T technology and also other related immunotherapeutic methods with promising performance, and highlighted how this therapy can affect the therapeutic outcome and next upsurge as a key clinical aspect of colorectal carcinoma. In this review, we recapitulate the current developments produced to improve the efficacy and specificity of CAR-T therapies in colon cancer.

Genome Editing with CRISPR-Cas9: A Budding Biological Contrivance for Colorectal Carcinoma Research and its Perspective in Molecular Medicine.

Genome editing is an addition, deletion, or replacement of a gene to remove or initiating explicit and preferred characters in the genome. Utilizing gene-editing tools like CRISPR-Cas9 technology could be accomplished either by gene-based methodology or protein-based technology that has been under scrutiny for the protracted time wherein physical techniques, viral and non-viral strategies have been utilized together. Transplanting ex vivo CRISPR edited cells empowers screening of single guide RNAs with high-throughput and CRISPR based screening in organoids transplantation to validate cancer cells including colorectal carcinoma in various phases of its development and treatment.CRISPR knockout screens have recognized genes that drive interest in colon cancer to develop hallmarks, especially in some cancer cell lines with single guide RNA, to disclose drug resistance mechanisms. One advantage of this method is to deal with CRISPR knockout genomic screening, which disrupts gene expression, rather than the partial knockdown that is mostly done with RNA interference and CRISPR/Cas technology. This technique is used to treat different forms of cancer because of its proficient editing of the target gene, along with the CRISPR/Cas system. Latest research has shown that the CRISPR/Cas gene-editing technique has theoretically reformed the expression in colorectal carcinoma of long non-coding RNA. For the next decade CRISPR/Cas9 technology will positively fuel the development of more in vivo gene editing clinical trials in colon cancer and will have an enormous impact on molecular medicine.

Implications of Klotho Protein for Managing Kidney Disease - an Emerging Role in Therapeutics and Molecular Medicine.

Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) are a growing public health problem. There is a paucity of sensitive biomarkers to detect AKI, early CKD, and ameliorate extra-renal complications. Klotho protein, detected mainly in the kidneys, regulates renal health and functions as a co-receptor for fibroblast growth factor 23 (FGF-23) signaling. It is now coming to be known for its extreme pleiotropic actions. These include cytoprotection via anti-oxidation, anti-senescence, anti-apoptosis, renoprotective effects, promotion of angiogenesis and vascularisation, inhibition of fibrogenesis, and stem cell preservation. Emerging clinical studies suggest kidney damage to be a perpetual state of renal Klotho deficiency. In AKI, Klotho levels in plasma and/or urine possibly will serve as an initial biomarker for kidney parenchymal injury. In CKD, Klotho levels may also be an indicator of early disease as well as predict the rate of progression. Earlier studies using ELISA as a technique reveal a correlation between plasma Klotho, eGFR, serum creatine, and Blood Urea Nitrogen (BUN) levels. Thereby preventing the decline of Klotho levels by various mechanisms can retard CKD advancement and improve renal function. Substantial data indicate Klotho can be therapeutically included as an individualized regimen for managing CKD patients. Considerable research is required in investigating the role of soluble Klotho as a biomarker in patients with different types and severity of kidney diseases, which will be highlighted in our review.

Understanding the Role of Corona Virus based on Current Scientific Evidence - A Review with Emerging Importance in Pandemic.

Coronavirus disease is a potentially deadly disease and of significant apprehension for global communal health because of its lethality. Vaccines and antiviral medications are still under trial to prevent or treat human coronavirus (HCoV) till date. The virus HCoV originated in 2003, SARS-CoV, which causes respiratory syndrome having distinctive pathogenesis and infections of the respiratory tract. A mechanism was projected for the evolution of SARS virus, and a handy association with bats was found. When this virus reaches the respective host system, the infection starts with spike protein binding to its complementary receptor of the host cell. The coronavirus spike protein's association with its host cell receptor complement is crucial in deciding the virus infectivity, tissue tropism and species variety. Recent studies show that SARS Coronavirus 2 or COVID-19 requires protease to get into cells, offering a new therapeutic target. Distinctive attention and exertions should be given to defending or reducing transmission in vulnerable populaces, including those directly associated with caregiving and treatment and also aged one. Researchers are planning to develop a vaccine for COVID-19, and in this approach are also considered developing a vaccine that sensitizes our immune system preventing from this pandemic. The present review focuses on the role of S-spike protein in COVID-19, which helps the virus intruding the enzyme ACE2 (Angiotensin-Converting Enzyme 2). Passive antibody therapy is an additional alternative to use blood donors from hale and hearty people who have already recovered from COVID-19 and therapeutic advancement in handling the COVID-19 pandemic.