High expression of CD9 and Epidermal Growth Factor Receptor promotes the development of tongue cancer.

Tongue cancer is distinguished by aggressive behavior, a high risk of recurrence, lymph, and distant metastases. Hypoxia-Induced Factor 1 α functions as a CD9 transcription factor. CD9 is a transmembrane protein that may be found on the cell membrane. It can modulate the expression of the Epidermal Growth Factor Receptor (EGFR) pathway. ELISA was used to measure serum CD9, p-EGFR, and p-Akt levels in 70 tongue cancer patients and 35 healthy controls. RT-PCR was used to analyze the gene expression of the related genes. The gene as well as protein expression of CD9, EGFR/p-EGFR, and Akt/p-Akt was significantly higher in case subjects when compared with the controls. The expression of CD9 was higher in case subjects who were smokers/alcoholics when to control subjects who were smokers/alcoholics. Overexpression of CD9 due to hypoxic conditions leads to the activation of EGFR-signaling pathway resulting in cancer progression, resistance to chemotherapy. Hence, CD9 could be a potential target to suppress cancer progression.

Association between iron profile status and insulin resistance in patients with type 2 diabetes mellitus.

Introduction: Individuals' burden of insulin resistance and metabolic syndrome, such as type 2 diabetes mellitus, is increasing. This indicates to intrigue into various facets of prevention, early screening, prognostication and feasible treatment alternatives in this arena. Aim: This study targets to evaluate iron profile status among people diagnosed with type 2 diabetes mellitus and normoglycemic in order to deduce association between iron parameters and insulin resistance, if any exist. Methodology: A case-control study of total 123 subjects, comprising males and females in the age group of 30 - 70 years were recruited for the study. Case group constituted 81 participants who were diagnosed with type 2 diabetes mellitus and control group constituted 42 healthy individuals who attended routine health check-ups in the hospital. Iron profile parameters including Serum Iron, Serum Ferritin, Total Iron binding Capacity and Glycemic profile parameter like fasting blood glucose, serum insulin were estimated. Transferrin saturation and HOMA-IR were calculated. Result: Ferritin and Transferrin saturation was found to be higher in cases than in controls with significance of p = 0.003 and p = 0.021 respectively and TIBC (total iron-binding capacity) was lesser in cases with p = 0.031. Comparison of Serum Iron values did not yield a significant result. Correlation study between ferritin and insulin resistance parameters yielded a satisfactory result in the cases (p<0.05) and controls (p<0.01) separately. Conclusion: This study implies that there is a clear link between iron profile status, notably ferritin, and the emergence of insulin resistance, and hence insulin production. This study supports the function of the micronutrient iron in the etiology of type 2 diabetes and its consequences.

AI-Based Homology Modelling of Fatty Acid Transport Protein 1 Using AlphaFold: Structural Elucidation and Molecular Dynamics Exploration.

Fatty acid transport protein 1 (FATP1) is an integral transmembrane protein that is involved in facilitating the translocation of long-chain fatty acids (LCFA) across the plasma membrane, thereby orchestrating the importation of LCFA into the cell. FATP1 also functions as an acyl-CoA ligase, catalyzing the ATP-dependent formation of fatty acyl-CoA using LCFA and VLCFA (very-long-chain fatty acids) as substrates. It is expressed in various types of tissues and is involved in the regulation of crucial signalling pathways, thus playing a vital role in numerous physiological and pathological conditions. Structural insight about FATP1 is, thus, extremely important for understanding the mechanism of action of this protein and developing efficient treatments against its anomalous expression and dysregulation, which are often associated with pathological conditions such as breast cancer. As of now, there has been no prior prediction or evaluation of the 3D configuration of the human FATP1 protein, hindering a comprehensive understanding of the distinct functional roles of its individual domains. In our pursuit to unravel the structure of the most commonly expressed isoforms of FATP1, we employed the cutting-edge ALPHAFOLD 2 model for an initial prediction of the entire protein's structure. This prediction was complemented by molecular dynamics simulations, focusing on the most promising model. We predicted the structure of FATP1 in silico and thoroughly refined and validated it using coarse and molecular dynamics in the absence of the complete crystal structure. Their relative dynamics revealed the different properties of the characteristic FATP1.

A Study of miRNA 223 Expression and its Correlation with Disease Severity in Chronic Plaque Psoriasis.

Background: Psoriasis is a chronic immune-mediated inflammatory disease affecting the skin and/or joints. MicroRNAs (miRNA) are single-stranded non-coding RNA molecules that bind to messenger RNA (mRNA) and regulate gene expression. Studies on peripheral blood mononuclear cells (PBMCs) in psoriatic patients showed an upregulation of miRNA 223. Aims and Objectives: a) To estimate and compare the expression of miRNA 223 in cases of chronic plaque psoriasis and controls. b) To correlate the expression of miRNA 223 with the severity of chronic plaque psoriasis. Materials and Methods: This study included 80 subjects (40 with psoriasis and 40 with age- and sex-matched healthy controls) attending the dermatology OPD of a tertiary care hospital from January 2018 to June 2019. A detailed history, determination of Psoriasis Area Severity Index (PASI) score and estimation of miRNA 223 by quantitative real-time polymerase chain reaction (qRT-PCR), was done in all subjects. Results: The expression of miRNA 223 (ΔCt) was higher in cases than in controls. The observed mean ΔCt was higher in severe (12.90 ± 0.46) than in mild (9.81 ± 1.70) and moderate (10.58 ± 1.26) psoriasis. The difference in expression of miRNA with varying severity of psoriasis was significant. The mean difference of ΔCt between mild to severe was (3.09) (P ≤ 0.001) and moderate to severe was (2.31) (P = 0.013). Among cases, the expression of miRNA 223 was higher in those exhibiting Koebner's phenomenon compared to those without Koebner's phenomenon (P = 0.0424). Conclusion: Expression of miRNA 223 was higher in psoriatic patients than in controls and the expression increased with the severity and activity of the disease suggesting the upregulation of miRNA 223 with the progression and activity of the disease.

Environmental pollutants and their effects on human health.

Numerous environmental contaminants significantly contribute to human disease, affecting climate change and public and individual health, resulting in increased mortality and morbidity. Because of the scarcity of information regarding pollution exposure from less developed nations with inadequate waste management, higher levels of poverty, and limited adoption of new technology, the relationship between pollutants and health effects needs to be investigated more. A similar situation is present in many developed countries, where solutions are only discovered after the harm has already been done and the necessity for safeguards has subsided. The connection between environmental toxins and health needs to be better understood due to difficulties in quantifying exposure levels and a lack of systematic monitoring. Different pollutants are to blame for both chronic and acute disorders. Additionally, research becomes challenging when disease problems are seen after prolonged exposure. This review aims to discuss the present understanding of the association between environmental toxins and human health in bridging this knowledge gap. The genesis of cancer and the impact of various environmental pollutants on the human body's cardiovascular, respiratory, reproductive, prenatal, and neural health are discussed in this overview.

Delineating the role of single-nucleotide polymorphism of CYP19 gene on aromatase activity in South Indian women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome is a common multifactorial endocrinopathy disorder affecting 5-15% of reproductive women worldwide. The CYP19 gene encodes key enzyme aromatase involved in androgen-to-estrogen conversion which plays a crucial role in the pathophysiology of the syndrome. Very few studies have been done in the Indian population; hence, we investigated whether CYP19 gene rs2414096 SNP is associated with PCOS and hyperandrogenism susceptibility in Karnataka women. METHODS: Three-hundred subjects including 150 PCOS and 150 age-matched controls were involved in the current case-control study. Sex hormones and biochemical estimation were performed by ELISA. Sanger sequencing and PCR-RFLP were used to genotype the SNP rs2414096. Genotypic-phenotypic association was studied. Statistical analysis was performed. RESULTS: The GG genotype was more common in patients, while the GA genotype was more common in control women. LH/FSH was significantly increased in GG genotype in PCOS when compared with AA and GA genotypes. Variations of CYP19 rs2414096 were not statistically significant with PCOS. CONCLUSION: CYP19 rs2414096 polymorphism was not associated with PCOS; however, the homozygous wild GG genotype may exhibit reduced aromatase activity with subsequent hyperandrogenism implicating endocrine abnormalities.

Association of pro-fibrinolytic receptor AnnexinA2 with tissue plasminogen activator/Inhibitor-1 in pre-eclampsia.

Background: The clinical manifestations of pre-eclampsia are related to placental anti-angiogenic factor alteration. These variations are mainly due to the alteration of plasminolytic components. The study aims to compare the expression of plasminolytic components in the placenta of women with and without pre-eclampsia. Material and Methods: The study included pregnant women with pre-eclampsia as PE group (n = 30) and without pre-eclampsia as a control group (n = 30). Placental bed biopsy tissues were collected. AnxA2, tPA, PAI-1 expression in the placental villous tissue was quantitatively evaluated using immunohistochemistry, western blot, and real time-PCR analysis. Results: The results of the study showed a significant decrease in the expression of ANXA2 and increased expression of tPA and PAI-1 in PE group compared to control group (p<0.005). AnxA2 expression showed positive correlation with tPA (r=+0.895, p=0.002) and negative correlation with PAI-1(r=-0.905, p=0.020) in control group whereas in the PE group AnxA2 expression was negatively correlated with tPA ((r=-0.801, p=0.016) and PAI-1 (R=-0.831, P=0.010). Conclusion: Decreased AnxA2 with increased expression of PAI-1 and tPA may be responsible for the altered fibrinolytic activity and play a significant role in pre-eclampsia pathogenesis.

Prognostic significance of tetraspanin CD9 and oncogenic epidermal growth factor receptor in tongue squamous cell carcinoma survival.

The most prevalent locations for head and neck cancer is the tongue. The surviving patients who are receiving therapy have considerably compromised speech, taste, chewing, and swallowing. CD9 is a cell surface protein that has contradictory role in cancer progression. The objective of the study is to analyze the Cluster of Differentiation 9(CD9), Epidermal Growth Factor Receptor (EGFR) and Phosphorylated Akt (p-Akt) expression in tongue cancer specimens and its clinical significance.50 tongue cancer sections were used to analyze the expression of CD9,EGFR and p-Akt by immunohistochemistry. Data regarding the histological grade of the tumor, age, sex, and habits were recorded, and relation with CD9,EGFR and p-Akt expression was assessed. Data were expressed as mean ± SEM. Categorical data was analyzed by Chi-square test. Student t-test was used to check the significance of data between two groups.A significant increase in the CD9,EGFR and p-Akt expression (1.8 ± 0.11, 2.06 ± 0.18 and 2.3 ± 0.15 respectively) was seen in the tongue cancer specimens. CD9 and p-Akt expression had a significant association with the histological grade (p < 0.004 and p < 0.006 respectively). CD9 expression was higher in patients with the combination of addiction/habit compared to patients with single addictions(1.08 ± 0.11 and 0.75 ± 0.47). Overall a poor rate of survival was observed in CD9 positive patients(p < 0.039). EGFR and p-Akt expression increased with increasing expression of CD9, suggesting its use as a biomarker to track the development of TSCC.

Fatty acid transport proteins (FATPs) in cancer.

Lipids play pivotal roles in cancer biology. Lipids have a wide range of biological roles, especially in cell membrane synthesis, serve as energetic molecules in regulating energy-demanding processes; and they play a significant role as signalling molecules and modulators of numerous cellular functions. Lipids may participate in the development of cancer through the fatty acid signalling pathway. Lipids consumed in the diet act as a key source of extracellular pools of fatty acids transported into the cellular system. Increased availability of lipids to cancer cells is due to increased uptake of fatty acids from adipose tissues. Lipids serve as a source of energy for rapidly dividing cancerous cells. Surviving requires the swift synthesis of biomass and membrane matrix to perform exclusive functions such as cell proliferation, growth, invasion, and angiogenesis. FATPs (fatty acid transport proteins) are a group of proteins involved in fatty acid uptake, mainly localized within cells and the cellular membrane, and have a key role in long-chain fatty acid transport. FATPs are composed of six isoforms that are tissue-specific and encoded by a specific gene. Previous studies have reported that FATPs can alter fatty acid metabolism, cell growth, and cell proliferation and are involved in the development of various cancers. They have shown increased expression in most cancers, such as melanoma, breast cancer, prostate cancer, renal cell carcinoma, hepatocellular carcinoma, bladder cancer, and lung cancer. This review introduces a variety of FATP isoforms and summarises their functions and their possible roles in the development of cancer.

Medium-Chain Fatty Acids and Breast Cancer Risk by Receptor and Pathological Subtypes.

Introduction: Medium-chain fatty acids contain 6-12 carbon atoms and are absorbed directly into the blood vessels, proceeding to the portal vein and, finally, to the liver, where they are immediately utilized for energy. We aimed to determine the medium-chain fatty acid levels in women with and without breast cancer. Materials and Methods: A total of 200 women (100 breast cancer subjects and 100 control subjects) were recruited for the study as per the inclusion and exclusion criteria. Blood samples were collected for biochemical estimations. Fatty acid methyl esters were isolated, and medium-chain fatty acid levels in plasma were analyzed using gas chromatography (GC-FID). Statistical analysis was performed using SPSS 20.0 software; p ≤ 0.05 was considered statistically significant. Results: The fatty acid analysis revealed a significant decrease in the levels of caprylic acid (C:8) and lauric acid (C:12) and a significant increase in the level of capric acid (C:10) in the breast cancer subjects when compared to the control group. The level of caproic acid (C:6) was not significantly increased in the breast cancer subjects. In particular, the HER2- and ER-positive breast cancer subjects showed a decrease in their caprylic acid and lauric acid levels compared to other receptors. Conclusions: The results of the current study imply that lower levels of caprylic and lauric acid may be associated with a higher risk of breast cancer. The relevance of medium-chain fatty acids for preventive and therapeutic interventions will be amplified by further research on the possibility that alteration in a patient's medium-chain fatty acid composition may mechanistically contribute to disease progression or breast cancer risk.

FOK l Vitamin D Receptor Gene Polymorphism and Risk of Dental Caries: A Case-Control Study.

The prevalence of dental caries in individuals who practice good oral hygiene increasingly indicates that other etiological factors, such as genetic factors, may be responsible for occurrence of caries, and its prevalence in younger individuals, such as adolescents, is an early manifestation of their genetic makeup. Therefore, there is a need to investigate the correlation of various genetic factors with the occurrence of dental caries in populations. Thus, this study assessed the relationship between single nucleotide polymorphism (rs2228570) in the vitamin D receptor gene and dental caries susceptibility. After obtaining ethical approval (NU/CEC/2020/0339), 377 adults, aged 18-40 years, were included in this study. Among the participants consenting to participate, salivary samples were collected, and an oral examination was conducted using the World Health Care Oral Health Survey Format 2013. The DMFT and PUFA index scores were recorded along with basic demographic details. The subjects were categorized as caries-free (controls, DMFT = 0) and caries-active (cases). The case group was further divided into the high-risk group (DMFT ≤ 10), moderate-risk group (DMFT = 4-9), and low-risk group (DMFT = 1-3). Saliva samples were used for vitamin D level analysis and DNA isolation. Polymerase chain reaction-based restriction fragment length polymorphism analysis using Fok1 digestion was performed on the isolated DNA. Salivary vitamin D levels were markedly higher in the caries-free group than in the caries-active group (p < 0.001). The T allele of rs2228570 was significantly associated with having active caries, while the C allele was associated with being caries-free. Individuals with the rs2228570 TC genotype had 2.814-fold increased likelihood, and individuals with the TT genotype had 3.116- fold increased likelihood of being caries-active. This finding is important in terms of patient counselling, as well as possibly in terms of prevention and treatment of caries.

Tetraspanin CD9: A friend or foe of head and neck cancer (Review).

Head and neck cancers are diverse and complex diseases characterised by unregulated growth of tumour cells in various parts of the head and neck region, such as in the buccal mucosa, floor of the mouth, tongue, oropharynx, hypopharynx, oesophagus, nasopharynx and salivary glands. Partial or total glossectomy, radiation or chemotherapy greatly affect patient quality of life. However, even following treatment, patients may relapse. Nicotine­derived nitrosamines and alcohol are the major etiological factors underlying this deadly disease. These compounds induce DNA damage that may lead to mutation in crucial genes, such as p53 and p21, which are important to regulate cell proliferation, thus leading to cancer. CD9 is a tetraspanin, which are a group of transmembrane proteins that have a role in cell motility and adhesion. The present review aimed to explore the role of CD9 in head and neck cancer. Epidermal growth factor receptor activity and cell proliferation are regulated by the CD9­integrin/CD9­transforming growth factor interaction. Hence, CD9 can play a dual role in various types of cancer.

Comparative study of not from concentrate and reconstituted from concentrate of pomegranate juices on nutritional and sensory profile.

Pomegranate juice is popular due to its unique health benefits, sensory characteristics and also a good source of bioactive compounds. Comparative study on processing effect of Not from Concentrate (NFC) and Reconstituted from concentrate (RFC) pomegranate juice on the nutritional and sensory characteristics of 'Ganesh' variant was conducted. Results showed that not much differences observed in parameters like pH, acidity, essential elements, protein, total sugars and polyphenol content between NFC and RFC. As per the study NFC had a better antioxidant activity with intracellular ROS inhibition of 11% higher with significant (p < 0.05) than RFC in HepG2 cell lines. Total anthocyanin content was significantly different (p < 0.05) in NFC (428.05 mg/l) compared to 326.74 mg/l in RFC expressed as cyanidin-3-glucoside. Iron uptake was 40 units (µg/mg protein) higher in NFC than RFC (p < 0.05) in HepG2 cells. Sensory flavor profile showed NFC having significant differences with respect to characteristic pomegranate freshness, fruitiness, sweetness and astringency mouthfeel. RFC had higher sweetish and cooked flavor with additional vegetable like notes of beet and carrot. Based on the data better antioxidant activity, iron bioavailability, anthocyanin content and sensory attributes were captured in pomegranate NFC juices over RFC juices.

Fatty acid desaturase 2 (FADS 2) rs174575 (C/G) polymorphism, circulating lipid levels and susceptibility to type-2 diabetes mellitus.

Several factors influence an individual's susceptibility in inter-individual lipid changes and its role in the onset of type-2 diabetes mellitus (T2DM). Considering the above fact, the present investigation focuses on determining the association between fatty acid desaturase 2 (FADS2) rs174575 (C/G) polymorphism, circulating lipid levels and susceptibility to type-2 diabetes mellitus. As per the inclusion and exclusion criteria a total of 429 subjects (non-diabetic-216; diabetic-213) were recruited for the study. Glycemic and lipid profile status were assessed using commercially available kits. Based on the previous reports SNP rs174575 of fatty acid desaturase gene (FADS2) was selected and identified using the dbSNP database. The amplified products were sequenced by means of Sanger sequencing method. Lipid profile status and apolipoprotein levels revealed statistically significant difference between the groups. Three models were assessed namely, recessive model (CC vs CG + GG), dominant model (CC + CG vs GG) and additive model (CC vs CG vs GG). The recessive model, displayed a statistically significant variations between the circulating lipid levels in T2DM. The multivariate model with genotype (G allele carriers), triglyceride (TG) and insulin served as a predictive model. The study results potentiate the functional link between FADS2 gene polymorphism, lipid levels and type-2 diabetes mellitus.

Fatty acids and their role in type-2 diabetes (Review).

Age, lifestyle and diet are major risk factors for the onset of type 2 diabetes mellitus (T2DM). Insulin resistance (IR) and ß-cell dysfunction underlie the pathophysiology of T2DM. Diabetic populations are also prone to lipid and lipoprotein abnormalities as an indirect effect of IR on key metabolic enzymes. However, recent studies suggested that lipid changes may not only be a consequence of impaired glucose metabolism but also a causative factor. Fatty acids (FAs) influence translocation of glucose transporters and insulin receptor binding and signalling, in addition to cell membrane fluidity and permeability. It is thus suggested that FAs may have an essential role in the development of IR and T2DM. Specific combinations of FAs within phospholipids and triglycerides were indicated to exhibit the strongest associations with the risk of T2DM. The aim of the present review was to investigate the role of FAs in the pathogenesis of T2DM, as it has yet to be fully elucidated.

ω-6/ω-3 fatty acid ratio as an essential predictive biomarker in the management of type 2 diabetes mellitus.

OBJECTIVES: Intake of dietary fatty acid may play a major role in the prevention and management of lifestyle-related diseases such as type 2 diabetes mellitus (T2DM). Therefore, the aim of this study was to find an association between ω-6 to ω-3 fatty acid ratio and T2DM. METHODS: Fasting plasma glucose, glycated hemoglobin, and insulin were measured using commercially available kits. Fatty acid methyl esters were prepared using standard protocols. Delta-5 desaturase (D5D) and delta-6 desaturase (D6D) activities were determined from product-to-precursor ratios of individual fatty acids in plasma. Statistical analysis was performed using SPSS version 20. RESULTS: The ratio of ω-6 to ω-3 was higher in the group with diabetes (13:1) when compared with the group without diabetes (4:1) and was statistically significant (P < 0.0001). Further association studies showed that univariate model with the ω-6 to ω-3 ratio and a multivariate model with D5D, D6D, and ω-6 to ω-3 ratio could serve as predictive polyunsaturated fatty acid pathway models for T2DM. CONCLUSIONS: From the study results, it is evident that ω-6 to ω-3 fatty acid ratios can serve as essential predictive biomarkers in the management of patients with T2DM. This would not only help in management but would also aid in prevention of increased T2DM incidence in India. These results potentiate the need to maintain an ideal balance of ω-6 to ω-3, as prevention is always better than cure.

Association of FADS2 rs174575 gene polymorphism and insulin resistance in type 2 diabetes mellitus.

BACKGROUND: Many risk factors contribute to the pathogenesis of diabetes. Gene and lifestyle factors are considered to be the major contributors. A dietary pattern is attributed to be one of the lifestyle risk factors favoring diabetes. The present study aims to find an association between fatty acid desaturase (FADS) gene polymorphism and glycemic profile in type 2 diabetes mellitus (T2DM). METHODOLOGY: A total of 429 subjects were included in the study on the basis of inclusion and exclusion criteria, of which 213 and 216 subjects were diabetic and control, respectively. Body mass index was calculated. Fasting plasma glucose, glycated hemoglobin (HbA1c) and insulin were measured using commercially available kits. rs174575 of FADS2 was selected based on previous publications and identified using the dbSNP database. To compare the biochemical parameters with the genotype, the following three models were used: additive model (CC vs CG vs GG), dominant model (CC + CG vs GG), and recessive model (CC vs CG + GG). RESULTS AND DISCUSSION: FBS, HbA1c, insulin, HOMA-IR, and HOMA-B exhibited a high and statistically significant difference between subjects and controls. The three models exhibited a statistically significant difference between FBS, HOMA-IR, and HOMA- B (p<0.05). CONCLUSION: The distribution of rs174575 genotype differed significantly between the subjects and controls in the present study. The study revealed that genetic variation in FADS2 is an additional facet to consider while studying the risk factors of T2DM.