Prevalence of hemoglobinopathies among Malayali tribes of Jawadhu hills, Tiruvannamalai district, Tamil Nadu, India: a community-based cross-sectional study.

BACKGROUND: Hemoglobin (Hb), a red pigment of red blood cells (RBCs), carries oxygen from the lungs to different organs of the body and transports carbon dioxide back to the lungs. Any fault present in the Hb structure leads to undesirable functional effects of the RBCs, such as sickle cell anemia (SCA), thalassemia, etc. Hemoglobinopathies affect around 7% of people in both developed and developing countries globally. The aim of the present study was to determine the prevalence and carrier frequencies of hemoglobinopathies including SCA, thalassemia, and other abnormal Hb variants among Malayali tribes in the Jawadhu hills of Tiruvannamalai district, Tamil Nadu, India. METHODS: A community-based cross-sectional study was carried out among 443 Malayali tribes inhabiting the Jawadhu hills of Tiruvannamalai district from July 2022 to September 2022. The RBC indices were analyzed using an automated 5-part hematology analyzer (Mindray, BC-5150) and hemoglobin fractions were done using the HPLC system (Bio-Rad, D-10) following standard protocols. FINDINGS: A total of 443 participants were screened, out of whom 14.67% had an abnormal Hb fraction, 83.30% were identified as normal, and 2.03% were borderline. Notably, the study revealed a prevalence of 0.68% for the α-thalassemia trait and 13.99% for the ß-thalassemia trait. INTERPRETATION: Haemoglobinopathies, specifically the ß-thalassemia trait, were most prevalent among the Malayali tribal population of Tamil Nadu residing in the Jawadhu hills of Tiruvannamalai district. Hence, we need special attention for creating awareness, increasing hemoglobinopathies screening programs, and improving the importance of tribal health conditions by the government and non-governmental organizations (NGOs) for the betterment of the ethnic tribes.

Allyl isothiocyanate regulates oxidative stress, inflammation, cell proliferation, cell cycle arrest, apoptosis, angiogenesis, invasion and metastasis via interaction with multiple cell signaling pathways.

Cancer growth is a molecular mechanism initiated by genetic and epigenetic modifications that are involved in cell proliferation, differentiation, apoptosis, and senescence pathways. Chemoprevention is an important strategy for cancer treatment that leads to blocking, reversing, or impeding the multistep process of tumorigenesis, including the blockage of its vital morphogenetic milestones viz. normal, preneoplasia, neoplasia, and metastasis. Naturally occurring phytochemicals are becoming ever more popular compared to synthetic drugs for many reasons, including safety, bioavailability, efficacy, and easy availability. Allyl isothiocyanate (AITC) is a natural compound present in all plants of the Cruciferae family, such as Brussels sprouts, cauliflower, mustard, cabbage, kale, horseradish, and wasabi. In vitro and in vivo studies carried out over the decades have revealed that AITC inhibits tumorigenesis without any toxicity and undesirable side effects. The bioavailability of AITC is exceedingly high, as it was reported that nearly 90% of orally administered AITC is absorbed. AITC exhibits multiple pharmacological properties among which its anticancer activity is the most significant for cancer treatment. Its anticancer activity is exerted via selective modulation of multiple cell signaling pathways related to oxidative stress, inflammation, cell proliferation, cell cycle arrest, apoptosis, angiogenesis, invasion, and metastasis. This review highlights the current knowledge on molecular targets that are involved in the anticancer effect of AITC associated with (i) inhibition of carcinogenic activation and induction of antioxidants, (ii) suppression of pro-inflammatory and cell proliferative signals, (iii) induction of cell cycle arrest and apoptosis, and (iv) inhibition of angiogenic and invasive signals related to metastasis.

Allyl isothiocyanate inhibits invasion and angiogenesis in breast cancer via EGFR-mediated JAK-1/STAT-3 signaling pathway.

Angiogenesis, invasion, and metastasis are the main events of cancer cells. JAK-1/STAT-3 is a key intracellular signaling transduction pathway, which controls the growth, differentiation, apoptosis, invasion, and angiogenesis of various cancer cells. The present study explored the impact of allyl isothiocyanate (AITC) on the JAK-1/STAT-3 pathway in DMBA-induced rat mammary tumorigenesis. The mammary tumor was initiated through a single dose of 25 mg DMBA/rat by a subcutaneous injection administered near the mammary gland. We observed decreased body weight and increased the total number of tumors, tumor incidence, tumor volume, well-developed tumor, and histopathological abnormalities in DMBA-induced rats that were modulated after being treated with AITC. Staining of mammary tissues showed a high accumulation of collagen in DMBA-induced rats and it was normalized by the AITC treatment. Moreover, DMBA-induced mammary tissues showed up-regulated expressions of EGFR, pJAK-1, pSTAT-3, nuclear fraction of STAT-3, VEGF, VEGFR2, HIF-1α, MMP-2, and MMP-9 and the down-regulated expressions of cytosolic fraction of STAT-3 and TIMP-2. Oral administration of AITC on DMBA-induced rats inhibits angiogenesis and invasion by modifying these angiogenic and invasive markers. The finding of the present study was further confirmed by molecular docking analysis that shows a strong binding interaction between AITC with STAT-3 and cocrystal structure of STAT-3 glide energy of -18.123 and -72.246 (kcal/mole), respectively. Overall, the results suggested that AITC inhibits activation of the JAK-1/STAT-3 pathway, which subsequently prevents angiogenesis and invasion. It was recommended that AITC might develop a beneficial effect against breast cancer.

Sickle cell anemia/sickle cell disease and pregnancy outcomes among ethnic tribes in India: an integrative mini-review.

Objective: To evaluate the studies which have reported the prevalence of maternal complications and outcomes for women with SCA/SCD. Healthy populations make a healthy community and improve the future for mankind. Pregnant women are an essential segment of humanity as they bear the fetus and supply nutrition for their development throughout the gestational period. Their health status and disease conditions also play a vital role in deciding the future of the offspring.Materials and methods: The Mesh terms: "Haemoglobinopathies" + "Sickle cell anemia" + "Sickle cell disease" + "Ethnic tribes" + "Pregnancy outcomes" + "India" were used to search the literature available from public databases such as "PubMed", "PubMed Central" "Google Scholar", "Science Direct" and "Scopus" and the same is checked for removing repetitions. The data was extracted and collected literature was thoroughly analysed. SCD/SCA is a commonly prevalent hereditary hemoglobinopathy disease and is related to augmented risk factors and premature mortality.Results: SCD severely affects pregnancy, which leads to the elevated occurrence of perinatal and maternal outcomes such as pre-eclampsia, eclampsia, abortions, intrauterine growth retardation (IUGR), etc., and sufficient care during the pregnancy guarantees an improved outcome. Due to the best health care conveniences, availability of drugs such as hydroxyurea, antibiotic prophylaxis, and vaccination, the life expectancy of SCD patients has greatly improved in recent times though directly related to the access and services available at the healthcare facilities for the needy and poor. Moreover, the latest innovations in the fields of prenatal screening and preimplantation genetic diagnosis (PGD), facilitate partners suffering from SCA/SCD to have a healthy child. There are no available studies on the prevalence of SCA/SCD in pregnant women among ethnic tribal populations from India.Conclusion: This review article is focused on the effects of SCA/SCD on pregnancy outcomes, the consistent follow-up, routine check-ups and successful management of complications throughout pregnancy, the various diagnostic methods toward preventive methods, curative and management therapeutic strategies and also defines the perinatal and maternal outcomes in the ethnic tribal populations of India.

Epidemiology and pathobiology of SARS-CoV-2 (COVID-19) in comparison with SARS, MERS: An updated overview of current knowledge and future perspectives.

Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the causative etiology of 'Corona Virus Disease-2019' (COVID-19); formerly referred as 'novel-Coronavirus-2019'. It was originated in Wuhan city, Hubei province, China in early December 2019. The World Health Organization (WHO) declared it as 'Public Health Emergency of International Concern' due to their rapid transmission and causing public and health-care-related casualties worldwide. This review provides an updated overview of COVID-19 (SARS-CoV-2), in comparison with the etiologies of the same group viz. SARS and MERS and also its future perspectives for planning appropriate strategies for prevention, control and treatment modalities to avert similar catastrophe in near future.

Particularly vulnerable tribal groups of Tamil Nadu, India: A sociocultural anthropological review.

"Adivasi" is the collective term for tribes, an indigenous population, and ethnic minorities of India. In general, tribal populations live in harmony with nature and resources within their habitat and largely reside in segregates in an unpolluted and natural environment away from modern civilization. As per the 2011 census, India contains 705 scheduled tribes (STs) and subtribes and 75 primitive tribal clusters. The ST population of Tamil Nadu, India, was found to be 794,697 and broadly spread in 38 districts constituting 36 tribes, among which 6 tribes were grouped as "particularly vulnerable tribal groups" (PVTGs), namely (1) Todas, (2) Kotas, (3) Kurumbas, (4) Irulas, (5) Paniyas, and (6) Kattunayakas, as the number of population in these tribal communities is either declining or remaining static. The state government is offering lots of benefit schemes for the STs, but they have not reached the tribal groups. Health problems of tribal communities have been profoundly influenced by different factors such as social, cultural, educational, economic, and political practices. The tribal peoples are exceedingly disease prone as they do not have access to basic health-care facilities. Therefore, concerned policymakers should focus on the changing health needs of tribal communities. In this regard, the current review article has been focused on the complete details (language, occupation, worship or deity, subdivisions or other names, etc.) of these six PVTGs and also to concentrate on the kind of problems they face while living in the societies. Therefore, the government and nongovernmental organizations need to find a way to improve their livelihoods and health status.

Monotonic Dose Effect of Bisphenol-A, an Estrogenic Endocrine Disruptor, on Estrogen Synthesis in Female Sprague-Dawley Rats.

Bisphenol-A (BPA) is a ubiquitous environmental chemical that produces adverse effect on reproduction system due to its potent estrogenic endocrine disruptive activity. The present study was aimed to investigate the monotonic dose effect of BPA on estrogen synthesis in female Sprague-Dawley rats. For this purpose, we administered three different doses of BPA (10, 50, 100 µg/kg bw/day) into rats and analyzed various biochemical, hormonal, molecular and histological parameters. 10 µg BPA treated rats showed significantly decreased levels of phase I detoxification agents (CYP450, Cyt-b5). Overexpression of eNOS with decreased expression of StAR and steroidogenic enzymes (CYP11A1, aromatase) indicate decreased production of estrogen. Increased levels of serum gonadotropins (FSH, LH) and decreased levels of estradiol suggest mimetic action of BPA and its feedback inhibition. Increased body weight, lipid profile status of 10 µg BPA treated rats and histological analysis of ovary and mammary tissue support the study. Overall, our results suggest that BPA exerts its estrogen mimetic effects in a monotonic manner.

Protective Effect of Allyl Isothiocyanate on Glycoprotein Components in 7,12-dimethylbenz(a)anthracene Induced Mammary Carcinoma in Rats.

The present study aimed to investigate the protective effect of allyl isothiocyanate (AITC) on glycoprotein components in 7,12-dimethylbenz(a)anthracene (DMBA) induced mammary carcinogenesis in female Sprague-Dawley rats. Mammary tumor was induced by a single dose of DMBA (25 mg/rat) injected subcutaneously near mammary gland. The levels of glycoprotein components such as hexose, hexosamine and sialic acid were analyzed colorimetrically in plasma, mammary and liver tissues. We observed an increased levels of glycoprotein components in plasma, mammary and liver tissues in cancer bearing rats. It was further confirmed by Periodic Acid Schiff staining in mammary and liver tissues. Upon oral administration of AITC to DMBA injected rats, the abnormal changes were reverted back to near normal levels and biochemical findings are supported by histological analysis. This could be due to the anti-neoplastic potential of AITC against DMBA-induced mammary carcinogenesis. The result shows that AITC has the potential to inhibit abnormal glycosylation that favors neoplastic transformation.

Effect of allyl isothiocyanate on NF-κB signaling in 7,12-dimethylbenz(a)anthracene and N-methyl-N-nitrosourea-induced mammary carcinogenesis.

BACKGROUND: Inflammation plays a pivotal role in the process of carcinogenesis and phytochemicals have anti-inflammatory properties gaining more importance in cancer chemoprevention. The present study aimed to investigate the anti-inflammatory effect of allyl isothiocyanate (AITC) on 7,12-dimethylbenz(a)anthracene (DMBA)- and N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis in female Sprague-Dawley rats. METHODS: RT-PCR and western blot analysis showed that inflammatory markers such as NF-κB p65, TNF-α, and IL-6 were overexpressed in mammary tumor tissues. Histological analysis of tumor tissues shows abnormality in hematoxylin and eosin (H&E) staining and toluidine blue (TB) staining of mast cell content, and lipid accumulation in oil red O staining. RESULTS: Administration of AITC (20 mg/kg bw) to carcinogen-injected rats significantly decreased the expression of NF-κB p65, TNF-α, and IL-6 in mammary tissues. Further, molecular docking study demonstrates the binding of AITC to NF-κB p65. Remarkably, AITC treatments control the growth of cancer cells as clearly evidenced by histopathological analysis. Staining of mammary tissues for mast cells and lipids indicates that AITC treatment to carcinogen-administrated rats significantly reduced mammary tumorigenesis. CONCLUSIONS: The result suggests that AITC has anti-inflammatory potential to prevent DMBA- and MNU-induced mammary carcinogenesis in rats.

Allyl isothiocyanate, a potent chemopreventive agent targets AhR/Nrf2 signaling pathway in chemically induced mammary carcinogenesis.

In the present study, we investigated the effect of allyl isothiocyanate (AITC) on liver detoxification signaling pathway in 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis. Mammary tumor was induced by a single dose of DMBA (25 mg/rat) injected subcutaneously near the mammary gland in Sprague-Dawley rats. DMBA-alone-treated rats show an increased synthesis of phase I detoxification enzymes, lipid peroxidative markers, liver marker enzymes, and lipid profiles whereas, depletion of phase II detoxification enzymes and antioxidants in rat liver tissues. Oral administration of AITC restored the levels of biochemical markers in DMBA-treated rats. Furthermore, histopathological results also confirmed that AITC protects DMBA-mediated hepatocellular damage. We also observed that AITC treatment significantly downregulates AhR and upregulates the expression of Nrf2 in DMBA-treated rats. The binding efficacy of AITC with AhR and Nrf2 analysis by molecular docking studies reveals that AITC has strong interaction with AhR and Nrf2 proteins through hydrogen and hydrophobic interactions. Thus, AITC prevents DMBA-induced mammary carcinogenesis via inhibition of phase I and induction of phase II detoxification enzymes by modulating AhR/Nrf2 signaling pathway.

Dose response chemopreventive potential of allyl isothiocyanate against 7,12-dimethylbenz(a)anthracene induced mammary carcinogenesis in female Sprague-Dawley rats.

The present study aimed to investigate the dose response chemopreventive potential of allyl isothiocyanate (AITC) against 7,12-dimethylbenz(a)anthracene (DMBA) induced mammary carcinogenesis in female Sprague-Dawley rats. Mammary tumor was induced by a single dose of DMBA (25 mg/rat) injected subcutaneously near mammary gland. We observed reduced body weight and increased in total number of tumors, tumor incidence and tumor volume in DMBA-induced rats. We also observed decreased antioxidant status (SOD, CAT, GPX and GSH) and increased lipid peroxidation (TBARS and LOOH) in plasma and mammary tissues. Increased levels of CYP450, Cyt-b5 and decreased levels of phase II (GST and GR) biotransformation enzymes noticed in liver and mammary tissues of DMBA-induced rats. Further, increased levels of lipid profile (TC, TG, PL and FFA) and lipoprotein (LDL and VLDL) were noticed. Whereas, decreased level of HDL in plasma and decreased levels of PL and FFA in mammary tissue. Oral administration of AITC different doses (10, 20 and 40 mg/kg bw) inhibited the tumor incidence and restored levels of biochemical markers. Biochemical findings are supported by histopathological studies. These results suggested that AITC at a dose of 20 mg/kg bw significantly exert chemopreventive potential against DMBA-induced mammary carcinogenesis.