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Background: Saraca asoca (Ashoka, family; Caesalpiniaceae) is an indigenous sacred tree, native to India. It has been used in various traditional medicinal systems and is one such plant that is highly therapeutic but its use in disease management is underrated in today’s era and has lost its importance. Objective: This narrative review is written to provide the information on medicinal importance of S. asoca and the significance of S. asoca in various traditional medicinal systems. Methods: Different databases were searched to gather information. Research articles, abstracts, and reviews are included in this review. Results: Saraca asoca is known for its unique pharmacological role in treating various uterine complications, menstrual disorders, and bacterial infections, bleeding hemorrhoids, urinary and dermatological problems. The stem bark of the tree is the principal constituent for treating menorrhagia and genito-urinary disorders. The stem bark, leaves, and seeds of S. asoca are known to contain flavonoids, tannins, alkaloids, glycosides, polyphenolics, fatty acids, and saponins. The reported major phytoconstituents responsible for its therapeutic uses are epicatechin, procyanidin B2, lyoniside, nudiposide, catechin, leucocyanidin, and leucopelargonidin. Various pharmacological activities of this plant are discussed in this review. Conclusion: It has been proved that Saraca asoca possesses several pharmacological properties and is useful in treating various diseases. More studies on quality control, standardization, and clinical trials on S. asoca should be performed, so that this plant could be utilized as an effective anti-cancer drug which could be a promising source for the herbal and pharmaceutical industry.

Background: Breast cancer is the most diagnosed cancer and the leading cause of mortality among women in India and worldwide. Reprogrammed glucose metabolism is considered as the hallmark of the cancer with immense therapeutic relevance. Withaferin A (WA), a phytocompound isolated from the plant Withania somnifera, commonly known as Ashwagandha has the remarkable anticancer role. However, the mechanism of action of WA in breast cancer metabolism is still unelucidated. Breast cancer cells have metabolic vulnerability and high glucose dependency. Thus targeting glycolysis could be the better therapeutic approach. Chemotherapy and radiotherapy have the side effects, to overcome this natural products can be used to treat cancer. The potential of natural compounds in targeting metabolic vulnerabilities of cancer and highlighting prospective therapeutic benefits that can be determined by improving our understanding of this field. Aims and Objective: To explore the therapeutic effect of WA in breast cancer cell lines and to identify the role of WA in targeting Warburg effect via c-myc. Cancer cells exhibit upregulated Warburg effect, to fulfill the bioenergetics and biosynthetic demands of the rapidly growing cancer cells. Thus targeting the Warburg effect could be the better therapeutic approach. Materials and methods: Breast cancer cell lines (MBA-MB-231, MBA-MB-468, MBA-MB-453 and MCF-7) were procured from NCCS Pune and maintained in DMEM media supplemented with 10% FBS. SRB dye was used for cell viability as it binds to the protein of the cells. Further Colony formation assay (using crystal violet dye) was done to evaluate the effect of WA on colony formation. Metabolic assays \ (lactate production, glucose uptake and ATP generation) were performed using kits (Eton Bioscience). Transient silencing using si-RNA of c-myc was done with lipofectamine 3000. Silencing of c-myc was done for Warburg effect and protein expression. RNA was isolated from breast cancer cells using Qaigen kit and RT-PCR was performed to evaluate the glycolytic gene expression before and after the treatment of the WA in breast cancer cell lines. To check the expression of glycolytic genes at protein level we had done the western blot. Protein isolation was done in RIPA lysis buffer and western blot was performed using primary antibodies of GLUT1, HK2, PKM2, c-myc. Statistical analysis was analyzed in graph pad prism. Breast cancer patient METABRIC data was analyzed and pathway deregulation score was calculated from Pathifier algorithm. Results: Withaferin A decreased the glucose uptake, lactate production and ATP production in different breast cancer cell lines. Further, WA induced suppression of key glycolytic enzymes via c-myc, decreased cell proliferation, biomass and colony formation ability of the breast cancer cells. Silencing of c-myc gene also showed the similar results to WA such as decrease in Warburg effect and reduction in glycolytic proteins expression. Through the LC-MS analysis WA decreases the key glycolytic metabolites and other pathway metabolites, induce metabolic catastrophe in breast cancer cells. Clinical relevance of our experiments was validated in dataset of ~2000 breast tumors (METABRIC) using Pathifier algorithm wherein we calculated deregulation score of glycolysis pathways in each of the tumor and normal sample. Importantly, higher deregulation of glycolysis was observed in breast tumor compared to normal tissues and found to be associated with poor prognosis. Conclusion: Our results highlight the anti- carcinogenic effect of Withaferin A in modulating breast cancer metabolism and the clinical significance of glycolysis in general. WA decreases the glucose metabolism and its flux through key metabolic pathways associated with the glycolytic intermediates. Therefore it could be argued that therapeutic targeting of breast cancer metabolism by WA may improve clinical outcome. Citation Format: Asifa Khan, Shumaila Siddiqui, Sheersh Massey, Daman Saluja, Syed Akhtar Husain, Mohammad Askandar Iqbal. Withaferin A induces metabolic crisis in breast cancer cell lines via decreasing c-myc expression: potential therapeutic implication [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-11-16.

Background: Breast cancer in the recent years has accounted to be most frequently reported cancer across the globe. Nearly 11.7% of total cancer cases were of breast cancer and 6,84,996 deaths were reported in the year 2020. Multiple endocrine neoplasia type 1 gene that encodes for menin protein is known be involved in numerous signaling pathways and is also reported to show its interactions with histone modifiers. MEN1 is frequently reported to be dysregulated in the cancer including neuroendocrine tumors, lung cancer and melanoma. However, the role of MEN1 in case of Breast cancer has not been well understood. Lifestyle, environmental conditions and ethnicity play crucial role in epigenetic modulation of gene expression. In the current scenario with high increase in number of cancer cases, there is need to develop more personalized course of treatment rather than generalized approach. Thus, discovery of new biomarkers will aid in designing better diagnostic and therapeutic strategy to treat cancer. Aims and Objective: In this study we aim to find MEN1 mRNA expression and its connection with the MEN1 promoter methylation in case of Indian breast cancer patients and to correlate our findings with the pathological parameters of the patients to understand the role of MEN1 gene in breast cancer progression. Material and methods: The ethical approval for the study was procured from Institutional ethical committee of AIIMS,New Delhi and Jamia Millia Islamia, New Delhi. The study comprises of 44 pair of Breast tissue samples including cancer and adjacent normal tissue collected at department of surgical oncology AIIMS, New Delhi and were stored in RNA later and PBS at -80˚C for RNA and DNA extraction respectively. DNA was extracted through PCI (Phenol-Chloroform-Isoamyl alcohol) method and was further confirmed by Agarose gel electrophoresis. TRIZOL method was used to extract RNA from tissue samples and was quantified using nanodrop. Moreover, cDNA synthesis was carried out using Verso cDNA synthesis kit. To investigate the MEN1 mRNA expression, RT- PCR was carried out with LightCycler96 SYBR Green I Master (Roche) using specific primers. To analyze the promoter methylation status of MEN1 promoter region, CT- conversion was done and MS-PCR was performed using Methylation and Unmethylation specific primers. Statistical analysis was done using Graph Pad and SPSS to correlate our findings with clinical parameters. Results: In our study we found 27 out of 44 patients to exhibit up-regulation of MEN1 mRNA in the breast cancer tissue as compared with the normal tisuue. MEN1 promoter unmethylation was detected in 25 out of 44 cases, which revealed its significant correlation with the upregulated MEN1 gene. Further on correlation of our data with the clinical parameters, we found its significant association with the estrogen receptor status and age of menopause of the patients. Conclusion: Our results of the MEN1 mRNA expression study and its association with MEN1 promoter methylation in case of breast cancer suggests the tumorigenic role of MEN1 in breast cancer. Our findings thereby indicate the possible role of MEN1 gene in progression of the disease. Further study on large sample size will aid in better understanding the role of MEN1 gene in Breast carcinoma. Citation Format: Sheersh Massey, Aasif Khan, Asifa Khan, SVS Deo, Syed Akhtar Husain. Promoter hypomethylation associated upregulation of MEN1 mRNA expression and its correlation with pathological parameters in Indian breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-18-02.

Background: In the past decade, a rising trend has seen in the use of plant-based medicines because of fewer/no side effects. Plants are always the major source of traditional medicines in every culture. The main objective of this review is to shed a light on phytochemical composition and pharmacological research of Valeriana wallichii. Methods: Electronic databases like Google Scholar, PubMed, Scopus, etc., were searched for traditional uses, extraction of phytoconstituents, therapeutical uses and pharmacology of V. wallichii. Results: V. wallichii has been used as a sleep remedy since ancient times in the Indian traditional system of medicines. It is also used as diuretic, spasmolytic and pain relieving agent. It is used for the treatment of epilepsy, dyspeptic symptoms, failing reflexes, habitual constipation, insanity, nervous debility, obesity, spastic disorders, and in snake poisoning, and also reported to have cytotoxic potential. The pharmacological activity of the plant is due to presence of different types of secondary metabolites, including valerianic acid, valerosidatum glycoside, valepotriates, dihydrovaltrate, 6-methylapigenin, hesperidin, sesquiterpenoids, bornylisovalerianate, isovalerenic acid, 1-camphene, 1-pinene, terpineol, valerianine, bornylisovalerianate, valerianine and so on. This review focuses on detailed phytochemistry of the plant and its therapeutic indication. The main emphasis is given on anticancer potential of V. wallichii, with in vitro cytotoxic as well as in vivo antitumor description. Conclusion: The review reveals that further research, as well as clinical trials, are needed to know this plant as an effective drug for the treatment of cancer in future with exact molecular mechanisms.

Abstract: The use of herbal medicines and supplements in the last thirty years has increased enormously. Herbal medication has demonstrated promising and effective potential against vari-ous diseases. Herbal and phytoconstituent medications are gaining popularity globally and many people are adopting herbal remedies to deal with different health issues. The indiscriminate use of antibiotics, due to the development of antimicrobial resistance, poses an unprecedented prob-lem for human civilization. Bacterial infections are difficult to cure because of the propensity of microbes to acquire resistance to a wide range of antimicrobial drugs. New compounds are being explored and quantified for possible antibacterial activity with little or no side effects. Research-ers are investigating the range of therapeutic plants mentioned in Unani, Ayurveda, and Siddha around the globe. Known and commonly acclaimed global databases such as PubMed, Research Gate, Science Direct, Google Scholar were searched using different search strings such as Indian medicinal plants, multidrug resistance (MDR), thin layer chromatography (TLC), antimicrobials, and Synergism were used in diverse combinations to reclaim numerous citations associated with this area. Thus, the current review aims to shed a light on the information of medicinal plants as a potential foundation of herbal drugs and elucidate how synergism and TLC bioautography play a crucial role in finding antimicrobial compounds.

Abstract: Nanoparticles have gained prominence in many areas and domains worldwide, such as metallic NP, carbon dots, quantum dots, polymeric NP, nano-suspension, nanocrystals, solid lipid nanoparticles (SLN), etc. and have been applied in the field of medicine as nanomedicine with promising results. Rise in cancer mortality rate has been an issue for a long time with female breast cancer as one of the most detected cancers. No permanent treatment has been developed till date could combat breast cancer with minimum side effects that are not long-lasting as there is no proper technique through which the anticancer drugs can recognize benign or malignant or normal cells that causes systematic toxicity. Advancement in technology has led to the discovery of many biological pathways and mechanisms. Tumor cells or cancer cells overexpress some high-affinity receptors that can be targeted to deliver the anticancer drugs at specific site using these pathways and mechanisms. Solid lipid nanoparticles (SLN) are among some of the excellent drug delivery systems, especially stealth SLN (sSLN). SLN, when conjugated with a ligand (called as sSLN), has affinity and specificity towards a specific receptor, and can deliver the drug in breast cancer cells overexpressing the receptors. Using this technique, various investigations have reported better anti-breast cancer activity than simple SLN (non-conjugated to ligand or no receptor targeting). This review includes the investigations and data on receptor-mediated targeting in breast cancer from 2010 to 2021 by searching different databases. Overall, information on SLN in different cancers is reviewed. In vivo investigations, pharmacokinetics, biodistribution, and stability are discussed to describe the efficacy of sSLN. Investigations included in this review demonstrate that sSLN delivers the drug by overcoming the biological barriers and shows enhanced and better activity than non-conjugated SLN which also verifies that a lesser concentration of drug can show anti-breast cancer activity. The efficacy of medicines could be increased with lower cancer deaths through stealth-SLN. Due to the low cost of synthesis, biocompatibility and easy to formulate, more study is needed in vitro and in vivo so that this novel technique could be utilized in the treatment of human breast cancer.

Abstract: Vitex negundo is a traditional herb known for its medicinal properties in Unani, Ayurveda, Siddha, Chinese, Roman, and other traditional systems of medicine. Traditionally, it is used as anthelminthic, antitoxin, aphrodisiac, contraceptive, antimalarial, analgesic, antiinflamatory, antiasthmatic, vermifuge, etc. All parts of V. negundo contain a number of phytoconstituents like alkaloids, fatty acids, flavonoids, glycosidic irridoids, lignans, phenols, steroids, tannins and di- and sesquiterpenes. Due to the presence of a variety of secondary metabolites, V. negundo is used in different types of diseases or disorders by traditional practitioners for the treatment of spermatorrhoea, stomachache, asthma, cold, diarrhoea, indigestion, gallstone, hernia, eye disorders, rheumatism, irritable bladder and dysmenorrhea, headache, migraine, kwashiorkor, neck gland sores, tubercular neck swelling, reddened, arthritis, jaundice, urticaria, eczema and liver disorders. It is most widely used for curing disorders of the reproductive system like vital power, depression, frail erection without libido, self-contempt for sexual abuse, stool containing prostatic fluid, and testicle pain. Facts were gathered from databases such as PubMed, Google Scholar, Springer, Scopus, and ScienceDirect, as well as literature found in books on medicinal plants. It has recently been reported to have cytotoxic properties against various types of cancer cells. It works by inducing apoptosis via the mitochondrial and TRIAL pathways and stopping the cell cycle. This review sheds light upon the ethnomedicinal uses, phytochemistry, different extraction procedures, and pharmacology of V. negundo. In conclusion, it was found that this traditional herb had an emerging past, exciting present and promising future for the treatment of several diseases.

This study evaluates the antibacterial activity and phytochemical characterizations of Andrographis paniculata extract (APE) and Berberis aristata extract (BAE). The stem of Andrographis paniculata (AP) and root of Berberis aristata (BA) were extracted with methanol. The results confirmed that APE and BAE possess high phenolic and flavonoid content. The antioxidant activity of the APE and BAE showed an elevated potential to scavenge DPPH (2,2-diphenyl-1-picrylhydrazyl) radicals with IC

Background CTCF encodes 11-zinc finger protein which is implicated in multiple tumors including the carcinoma of the breast. The Present study investigates the association of CTCF mutations and their expression in breast cancer cases. Methods A total of 155 breast cancer and an equal number of adjacent normal tissue samples from 155 breast cancer patients were examined for CTCF mutation(s) by PCR-SSCP and automated DNA sequencing. Immunohistochemistry (IHC) method was used to analyze CTCF expression. Molecular findings were statistically analyzed with various clinicopathological features to identify associations of clinical relevance. Results Of the total, 16.1% (25/155) cases exhibited mutation in the CTCF gene. Missense mutations Gln > His (G > T) in exon 1 and silent mutations Ser > Ser (C > T) in exon 4 of CTCF gene were analyzed. A significant association was observed between CTCF mutations and some clinicopathological parameters namely menopausal status (p = 0.02) tumor stage (p = 0.03) nodal status (p = 0.03) and ER expression (p = 0.04). Protein expression analysis showed 42.58% samples having low or no expression (+), 38.0% with moderate (++) expression and 19.35% having high (+++) expression for CTCF. A significant association was found between CTCF protein expression and clinicopathological parameters include histological grade (p = 0.04), tumor stage (p = 0.04), nodal status (p = 0.03) and ER status (p = 0.04). Conclusions The data suggest that CTCF mutations leading to its inactivation significantly contribute to the progression of breast cancer.

Background: Cytokines are the key regulator molecules that modulate immune response. Tumor necrosis factor (TNF- α-308 G/A and TNF-β +252 A/G ) are inflammatory cytokine that control the progression of several types of cancer. They play a vital role in both tumor progression and destruction based on their concentrations. The role of TNF-α-308 G/A and TNF-β +252 A/G gene polymorphism in the etiology of breast cancer (BC) is not clearly understood. Therefore, present study investigates the association of TNF-α -308 G/A and TNF-β +252 A/G and the clinical features with Breast cancer patients. Methods: In a case- control study, we have investigated 150 breast cancer patients and 300 age and ethnically matched healthy controls for duration of 3 years from North India. Promoter polymorphisms of tumor necrosis factor gene (TNF-α -308 G/A and TNF-β +252 A/G) were genotyped using allele specific oligonucleotide polymerase chain reaction ASO and restriction fragment length polymorphism (PCR-RFLP). The associations were evaluated by calculating the pooled odds ratio (OR) with 95% confidence interval (95% CI) using SPSS. Results: Patients with different clinico-pathological variables and healthy controls were analyzed. Significant association was observed in A allele of TNF-α -308 G/A in breast cancer patients as compared to healthy controls (p

Lacunae exist in the molecular event(s) specificity associated with cervical cancer (CaCx) pathogenesis. The present study aimed to evaluate the significance of telomerase-cervical cancer stem cells (CSCs) modulation in CaCx pathogenesis with underlying HPV16 infection. The study included HPV16 positive cases only (N = 65) of the total enrolled cases from Northeast India. The analysis of viral load and the differential messenger RNA expression of E6, E7, hTERT, hTR, and cancer stem-cell markers was studied by real-time polymerase chain reaction. Further the protein and colocalization study for E6, hTERT, and oct4 was performed by immunofluorescence. The real-time polymerase chain reaction based analysis showed an upregulation of HPV16 viral oncoprotein E6 and E7, and telomerase component hTERT and hTR expression and their correlation in CaCx susceptibility and severity. The hTERT expression correlated with viral load; while the E6 and telomerase protein expression colocalized in the nucleus. The CSCs marker octamer-binding transcription factor 4 (OCT4) was significantly upregulated in CaCx cases, was associated with CaCx susceptibility and severity, and colocalized with E6 expression in the nucleus as revealed from the immunofluorescence studies. To conclude, the telomerase-OCT4 axis modulation holds key in HPV16 CaCx pathogenesis mediated by HPV16 E6 viral oncoprotein expression, and underlines its potential for therapeutic targeting.

In the present study, nontoxic selenium nanoparticles were synthesized extracellularly using probiotic bacteria Lactobacillus acidophilus. The synthesized Lactobacillus acidophilus mediated selenium nanoparticles (LA-SeNPs) show the surface plasmon resonance (SPR) at 385 nm. The hydrodynamic radius of LA-SeNPs was found to be 34.13 nm along with polydispersity index (0.28) and zeta potential (+ 37.86 mV). TEM shows that the average diameter of LA-SeNPs is 2–15 nm. FTIR suggest that extracellular proteins present in bacterial culture were responsible for reduction and stabilization of Se ions to LA-SeNPs. The antibacterial activity of synthesized nanoparticles was studied against five different sensitive and resistant bacterial strains. The MIC90 for bacterial strains were in the range ± 1 to ± 10 µg/ml. The inhibition and degradation of bacterial biofilm were studied against all the tested strains. The synthesized nanoparticles were cyto-compatible against human HEK-293 normal cell lines shown by MTT assay.

The metabolism of cancer is remarkably different from that of normal cells and confers a variety of benefits, including the promotion of other cancer hallmarks. As the rewired metabolism is a near-universal property of cancer cells, efforts are underway to exploit metabolic vulnerabilities for therapeutic benefits. In the continued search for safer and effective ways of cancer treatment, structurally diverse plant-based compounds have gained substantial attention. Here, we present an extensive assessment of the role of phytocompounds in modulating cancer metabolism and attempt to make a case for the use of plant-based compounds in targeting metabolic vulnerabilities of cancer. We discuss the pharmacological interactions of phytocompounds with major metabolic pathways and evaluate the role of phytocompounds in the regulation of growth signaling and transcriptional programs involved in the metabolic transformation of cancer. Lastly, we examine the potential of these compounds in the clinical management of cancer along with limitations and challenges.

BACKGROUND Cyclin D1 (CCND1) polymorphisms, a regulator of the cell cycle progress from G1 to the S phase, may lead to uncontrolled cell proliferation and lack of apoptosis. G870A, a common single-nucleotide polymorphism in CCND1 influences breast cancer risk. However, the association between G870A polymorphism and breast cancer risk is ambiguous so far. MATERIALS AND METHODS In this case-control study, we analyzed the role of G870A polymorphism with breast cancer risk in Indian women. A meta-analysis of 18 studies was also performed to elucidate this association by increasing statistical power. RESULTS In our case-control study, significant risk association of the CCND1 G870A AA genotype with breast cancer in total cohort (odds ratio [OR], 2.98; 95% confidence interval [CI], 1.64-5.42; P value, 4.96e-04) and premenopausal women (OR, 3.31; 95% CI, 1.54-7.08; P value, .003) was found. The results of the meta-analysis showed that AA genotype of the CCND1 G870A polymorphism significantly increases breast cancer risk in total pooled data (AA vs GG+GA: OR = 1.20; 95% CI = 1.03 to 1.39; P value, 0.016*) and Caucasian (AA vs GG+GA: OR = 1.22; 95% CI = 0.99 to 1.51; P value, .056*) but not in Asian population. Further, a significant protective association with breast cancer was also found in the GA vs AA comparison model in pooled data (OR = 0.73; 95% CI = 0.58 to 0.92; P value, .007*) as well as in Caucasian subgroup (OR = 0.62; 95% CI = 0.49 to 0.94; P value, .022*). CONCLUSION CCND1 G870A AA genotype was found associated with breast cancer risk. Future association studies considering the environmental impact on gene expression are required to validate/explore this association.

BACKGROUND Pregnant women infected with HEV develops adverse pregnancy outcomes like, abortions, intrauterine fetal death, still births, neonatal deaths, preterm delivery and maternal mortality. AIM To correlate oestrogen and its receptors ESR1α and ESR2β levels with HEV-associated feto-maternal outcomes. MATERIAL & METHODS A total of 142 pregnant women with HEV infection and 142 pregnant controls were included in study from Department of Obstetrics & Gynaecology and Department of Medicine, Maulana Azad Medical College (MAMC) and associated Lok Nayak Hospital (LNH), New Delhi. Three millilitre of blood sample was collected in plain for quantification of oestrogen, and its receptors ESR1α and ESR2β using commercially available third-generation ELISA kits. RESULTS The levels of oestrogen, ESR1α and ESR2β were considerably higher in HEV-infected pregnant women (20.11 ± 18.19 ng/mL, 10.58 ± 3.27 ng/mL, 10.42 ± 4.71 ng/mL respectively) than pregnant controls (11.74 ± 6.42 ng/mL, 9.11 ± 1.63 ng/mL, 9.01 ± 1.18 ng/mL respectively)(P

Background LATS2, a presumed tumor suppressor gene located on chromosome 13q11–12 is involved in cell growth related activity like regulation of cell cycle at G1/S. The reduced expression of LATS2 has been reported in many tumors; including tumors of Breast, which is to the best of our knowledge has not been studied in north Indian female breast cancer population. Objective Here, we looked upon the expression pattern and methylation status of the LATS2 gene in north Indian female breast cancer cases to further strengthen its role as a tumor suppressor gene and more importantly as a cancer biomarker. Methods mRNA expression level was determined by real time PCR in 140 Breast cancer patients, Protein expression was studied by Immunohistochemistry and Promoter methylation was studied by Methylation specific PCR. All findings were correlated with clinicopathological features. Results LATS2 mRNA expression was remarkably downregulated in 67.85% (95/140) cases. The expression of Large Associated Tumor Suppressor 2 at protein level was also absent in 67.85% (95/140) cases. The absence of LATS2 protein strongly correlated with promoter hypermethylation where 91 out of a total of 107 hyper methylated cases showed absence of protein (91/107, 85%). The absence of LATS2 protein was strongly significant with HER2 neu status (0.01), TNM staging (0.009) and Molecular subtype (0.024). Conclusion The decreased expression in breast cancer seems to be associated with hypermethylation of LATS2 promoter regions. Further LATS2 as a tumor suppressor can be recognized as a promising Biomarker in Breast cancer pathogenesis. Though, further studies, targeting larger sets of breast cancer population are required to establish LATS2 as a promising biomarker.

Hepatitis B with precore stop codon mutation is related with severe liver damage in HBeAg negative patients. It is of utmost importance to screen the G1896A precore mutation. The study was designed to assess the impact of G1986A mutations in patients with different clinical spectra of the liver disease by PCR–LCR. 210 HBV positive patients with HBeAg negative serology of different kind of liver diseases (AVH = 72, FH = 21, CH = 79, Cirrhosis = 20 and HCC = 18) were screened. Patients were screened for the presence or absence of precore G1896A mutation by PCR–LCR. Direct nucleotide sequencing was done to confirm the results of LCR. Precore mutant in HCC was 94.4% (17/18), 85.7% (18/21) in FH, 60% (12/20) in liver cirrhosis, 48.1% (38/79) in chronic hepatitis and 27.7% (20/72) in AVH cases. The serum ALT level was statistically significant between HBeAg negative WT and G1896A mutants in chronic hepatitis cases. ALT level and HBV DNA level was slightly raised in the pre core mutant but and was not significant. Genotype D had a higher prevalence (79.5%) as compared to genotype A (20.5%). The mutations detected by PCR–LCR were in 100% concordance with direct sequencing. The exceptionally high prevalence of G1896A in FH and HCC demonstrates that the precore mutants are strongly associated with the progression of liver diseases in patients with HBeAg negative serology. The findings are also suggestive of screening HBV precore G1896A mutation particularly in HBeAg negative cases. The precore G1896A mutation increases proportionately in severe form of liver diseases. LCR can be a suitable tool for screening of G1896A mutations. Keywords: Hepatitis B, G1896A, Mutation, Ligase chain reaction, Direct sequencing, Serology

Fascioliasis is caused by Fasciola species transmitted by freshwater Lymnaeidae snails and infecting herbivorous mammals and humans worldwide. In southern Asia, fascioliasis is a problem in livestock from the Near East to Bangladesh, where recent human infection reports are worrying. In this region, Fasciola gigantica is transmitted by species of the Radix auricularia superspecies group. In the densely populated northern Indian state of Uttar Pradesh, livestock appears infected throughout. The economic importance of buffaloes highlights the need to control their very high infection rates. In the Gorakhpur area, a molecular method based on the two specific primer sets of genomic DNA was applied to fasciolids from buffaloes slaughtered in local abattoirs and cercariae from R. acuminata snails from freshwater collections. PCR products and sequences demonstrated that the cercariae belonged to F. gigantica and that R. acuminata acts as vector for its transmission to buffaloes. The 72.0% rate found in one transmission focus appears to be the highest worldwide record of fasciolid infection in a lymnaeid population. Lymnaeid prevalences and burdens found close to human communities indicate a very high infection risk. This method is simple, fast and cheap because there is no need for sequencing, it differentiates between fasciolid species and between fasciolids and other trematodes infecting R. acuminata, facilitates epidemiological surveys, and is useful for surveillance to evaluate the efficiency of control measures. Within climate change predictions, future increases of rain events and floods suggest the need for control and surveillance efforts in this endemic area.

The metabolism of cancer is remarkably different from that of normal cells and confers variety of benefits including the promotion of other cancer hallmarks. As the rewired metabolism is a near-universal property of cancer cells, efforts are underway to exploit metabolic vulnerabilities for therapeutic benefit. In the continued search for a safer and effective ways of cancer treatment, structurally diverse plant-based compounds have gained substantial attention. Here, we present an extensive assessment of the role of phytocompounds in modulating cancer metabolism and make a case for the use of plant-based compounds in targeting metabolic vulnerabilities of cancer. We discuss the interactions of phytocompounds with major metabolic pathways and evaluate the role of phytochemicals in the regulation of growth signaling and transcriptional programs involved in metabolic transformation of cancer. Lastly, we examine the potential of these compounds in clinical management of cancer along with limitations and challenges

Background Runt related transcription factor3 (RUNX3) is considered as a tumor suppressor gene (TSG) that functions through the TGF-β dependent apoptosis. Promoter methylation of the CpG islands of RUNX3 and overexpression of enhancer of zeste homolog 2 (EZH2) has been suggested to downregulate RUNX3 in cancer. Methods Here, we studied the expression of RUNX3 and EZH2 in 58 esophageal tumors along with paired adjacent normal tissue. mRNA levels, protein expressions and cellular localizations of EZH2 and RUNX3 were analyzed using real-time PCR and immunohistochemistry, respectively. DNA methylation was further assessed by the methylation specific-PCR. Results Compared to normal tissue, a significant increase in expression of RUNX3 mRNA in 31/57 patient’s tumor tissue (p p = 0.002). 22 of the 27 unmethylated cases at the promoter region of the RUNX3 had elevated RUNX3 protein expression (p Conclusion The data presented in this study provide new insights into the biology of RUNX3 and highlights the need to revisit our current understanding of the role of RUNX3 in cancer.

BackgroundAs per WHO, Cervical cancer (CaCx) is a global issue, being the fourth common cancer in women with incidence rate of 13.1 per 1 lakh women globally and accounting for 311000 deaths in the year 2018 itself globally. The molecular pathogenesis in Human papillomavirus (HPV) infected cases is inconclusive. The detection of molecular factors leading to progression of CaCx can be important in the diagnosis and management of the disease. p53 a known tumor suppressor gene having a regulative role in cell cycle has been highlighted as key factor in the prevention of cancer but its significance in CaCx cases has been variably documented. The present study therefore targeted to evaluate the significance of p53 profile in CaCx cases in ethnically distinct northeast Indian population.MethodsBlood and Tissue samples (N = 85) of cervical cancer patients were collected and screening for HPV was performed using PCR. Thereafter the differential mRNA expression(qPCR), Immunohistochemistry, Mutation (PCR direct sequencing method) of p53 was studied. Further p53 epigenetic profiling was done by Methylation specific PCR (MS-PCR) and western blotting by using p53 acetylation specific antibodies.ResultsOur findings revealed that the downregulation of p53 was associated with the progression of disease and the variation in downregulation based on p53 polymorphism was observed. Further hypermethylation and deacetylation of p53 was also found to be associated with the pathogenesis of CaCx. The downregulated expression and hypermethylation of p53 in lower grade of CaCx, together established its association with the progression of CaCx from lower to severe grade.ConclusionTherefore, in CaCx patients of northeast Indian population, malfunctioning of p53 is found to have significant role in cervical cancer progression.

Background: Genetic changes in p53 gene contribute to breast cancer susceptibility. Objective and Methods: A case-control study and a meta-analysis were performed to investigate the role of p53 codon72 SNP with breast cancer susceptibility in Indian women. Results: p53 heterozygous arginine variant was associated with decreased risk of breast cancer in total cohort. In meta-analysis, Allelic and GG vs. CC genetic comparison model were found to be associated with breast cancer risk. Moreover, recessive comparison model indicated a protective correlation with breast cancer occurrence. Conclusion: The findings of our case-control study and meta-analysis suggest a significant association between p53 Arg72Pro polymorphism and an increased risk of breast cancer in Indian population.

Background & objectives: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality. The objective of this study was to find out the differential expression of apolipoproteins (ApoAI and ApoAIV) in HCC and cases of liver cirrhosis and chronic hepatitis (controls) without HCC and to compare ApoAI and ApoAIV expression with alpha-foetoprotein (AFP), the conventional marker in HCC. Methods: Fifty patients with HCC and 50 controls comprising patients with liver cirrhosis (n=25) and chronic hepatitis (n=25) without HCC were included in this study. Total proteins were precipitated using acetone precipitation method followed by albumin and IgG depletion of precipitated protein using depletion kit. Proteins were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The expression changes of ApoAI and ApoAIV were confirmed by western blotting using specific primary and secondary polyclonal antibodies followed by densitometric protein semi-quantitative estimation. ApoAI, ApoAIV and AFP were measured in the plasma samples by ELISA method. Results: Semi-quantitative densitometric image analysis of the western blot images and the comparison between HCC patients with those without HCC (control) revealed differential expression of ApoAI and ApoAIV. Levels of ApoAI were significantly higher in patients with HCC compared to controls without HCC (0.279±0.216 vs 0.171±0.091 and 0.199±0.014; P

Ethnopharmacological relevance Synthetic drugs used for cancer treatment have side effects that may be immunosupressive, can cause liver, kidney and cardiac toxicity, and infertility and ovarian failure, among others. Thus, herbal drugs could be used in the cancer treatment as an adjuvant therapy. Andrographis paniculata (Burm.f.) Nees (AP) is one of the traditional herbs used in different alternative medicinal systems such as Ayurveda, Unani, Chinese, Malayi, Siddha, etc. for the treatment of various disorders and diseases including cancer. Aim of the study The aim of writing this review is to highlight the medicinal importance of AP and its main phytoconstituent andrographolide (AG). The main emphasis was given on the anticancer activity of AG, its proposed mechanisms of action, novel approaches used to improve its biopharmaceutical properties with the perspective of evidence-based research, and its development as an adjuvant therapy for cancer treatment in future. Materials and methods Literature survey was conducted and research papers were retrieved from different databases such as Pubmed, Google Scholar, ACS, Wiley online library, ScienceDirect, Springer, and Scopus during 1970–2020. Research articles, review articles, and short communications, etc. were used for this purpose. The papers were selected on the basis of exclusion and inclusion criteria. Results Different anticancer mechanisms of AG have been reportedly proven such as cell cycle arrest, apoptosis, NF-κβ inhibition, antiangiogenesis, cytokine inhibition, etc. whereas its pharmacokinetic properties showed its highly protein bound nature, Cyt P400 (CYP) inhibition, low aqueous solubility, poor oral bioavailability, etc. Different novel formulations of AG have been investigated to increase its bioavailability for better efficacy. Conclusion This review can provide knowledge about the potential applicability of AP or AG as an adjuvant therapy in cancer treatment. Further research is needed before making any conclusion about the efficacy in humans as an adjuvant therapy in cancer.

Background: Bacopa monnieri (BM) is a herbaceous plant traditionally used from time immemorial in Ayurvedic and folklore medicines. We hypothesized that the extract of the whole plant might contain numerous molecules with having antitumor activities that could be very effective in killing of human cancer cells. Objectives: This work investigated anticancer activity of bioactive fraction of BM. Materials and Methods: The hydroalcoholic extract of BM was fractionated with different solvent, namely, hexane, dichloromethane (DCM), acetone, methanol, and water. The in vitro anticancer activity was performed against various Human Cancer Cell lines, namely, Colon (HT29, Colo320, and Caco2), Lung (A549), Cervix (HeLa, SiHa), and Breast (MCF-7, MDAMB-231). Further, DCM fraction was evaluated in vivo for anticancer activity against Ehrlich ascites carcinoma (EAC) tumor-bearing mice since it showed the best cytotoxicity at 72 h (IC50 41.0–60.0 µg/mL). The metabolic fingerprinting of these extract were carried out using high-performance thin-layer chromatography along with quantification of bacoside A, bacoside B, cucurbitacin B, cucurbitacin E, and bittulinic acid. Results: Oral administration of DCM fraction at a dose of 40 mg/kg rendered prominent reduction of tumor regression parameters such as tumor weight, packed cell volume, tumor volume and viable tumor cell count as compared to the untreated mice of the EAC control group. The anticancer activity of DCM fraction may be due to the presence of large amount of bacoside A, B and cucurbitacins. The molecular docking studies of major metabolites with targeted proteins predicted the anticancer activity of DCM fraction which was in support of in vivo activity. Conclusion: The in vitro, in vivo, analytical and in silico studies on DCM fraction of Bacopa monieri has proved its great potential for development of anticancer phytopharmaceuticals. SUMMARY A new HPTLC method has been developed and validated for the qualitative and quantitative analysis of bacoside A, B, cucurbitacin B, D, E and bittulinic acid in Bacopa monnieri extract. Enrichment of active anticancer metabolites was done by polarity based fractionations of hydroalcoholic extract of Bacopa. DCM fraction of a hydroalcoholic extract of Bacopa showed anticancer potential against human cancer cell line (IC50 41.0-60.0 µg/mL) and in EAC treated mice (at a dose of 40 mg/kg body weight). The anticancer activity of Bacopa may be due to the presence of bacosides and cucurbitacin and it was confirmed by in silico screening. Abbreviations used: DBM: DCM fraction of Bacopa monnieri; DCM: Dichloromethane; EAC: Ehrlich ascites carcinoma; HCT: Hematocrit; HGB: Hemoglobin; HPTLC: High performance thin layer chromatography; ICH: International council for Harmonisation; LOD: Limit of detection; LOQ: Limit of quantification; LYM: Lymphocytes; MCH: Mean corpuscular hemoglobin; MCHC: Mean corpuscular haemoglobin concentration (MCHC); MCV: Mean corpuscular volume; MTT: 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PLT: Platelet; RBC: Red blood cell; RDW: Red blood cell distribution width; RSD: Relative standard deviation; WBC: White blood cells.

The basis of host response in hepatitis E virus (HEV)—related liver disease during pregnancy—is still unclear. The study aims to evaluate anthropometric parameters and biochemical nutritional parameters in hepatitis E infection during pregnancy and correlate it with severity of the disease. A total of consecutive 267 pregnant women with jaundice were recruited. The jaundiced patients were classified as acute viral hepatitis (AVH) or acute liver failure (ALF). The study group included 144 pregnant women with HEV infection and 144 healthy asymptomatic age and gestational age-matched pregnant women as controls. Nutritional factors were evaluated on basis of anthropometric parameters and biochemical factors. Serum prealbumin and folate were assayed by ELISA kit. All nutritional parameters were significantly lower in pregnant women with HEV infection as compared with healthy pregnant controls. Some of the nutritional parameters significantly lower in ALF pregnant patients compared to AVH pregnant patients in HEV group. Linear regression analysis of the AVH group showed that serum total protein and mid-upper arm circumference (MUAC) were significant predictors for bilirubin, body mass index (BMI) could significantly predict viral load level, and total protein, prealbumin, folate, and tricep skin fold thickness (TSFT) could significantly predict prothrombin time. In ALF group, serum prealbumin could significantly predict bilirubin levels and MUAC could significantly predict prothrombin time. Malnutrition might confer a higher predisposition for HEV infection during pregnancy and is associated with increased severity of disease in terms of occurrence of ALF.

BACKGROUND: Cervical cancer is the most common cancer in Indian women. Infection with a high-risk human papillomavirus (HR-HPV) is the greatest risk factor for developing cervical cancer. The genetic and epigenetic changes in the tumor suppressor p16 gene is play an important role in the development of cervical cancer. OBJECTIVE: To evaluate the expression and promoter methylation of p16 gene in HR-HPV infected squamous cell carcinoma of the uterine cervix. METHODS: To find out p16INK4a expression and methylation status 105 squamous cell carcinoma of the uterine cervix were investigated by using immunohistochemistry and Methylation Specific PCR techniques. RESULTS: HPV16/18 was amplified in 83.8% cases of the cervix. 80% of them were positive for HPV type 16, while only 3.8% were positive for HPV type 18. Promoter CpG island hypermethylation of p16 gene was detected in 20.9% tissue samples of cervical carcinoma. Of these hypermethylated samples 90.9% cases showed nil/very low p16INK4a expression (P = 0.001). Overexpression of p16INK4a was observed in 73.3% cases of HR-HPV infected squamous cell carcinoma of the cervix. CONCLUSION: An association between p16 methylation, expression, and HR-HPV infection suggested the compliance of HPV infection and aberration of p16 gene have a synergic effect on initiation and progression of cervical carcinoma.

Background Craniofacial bone loss is a common phenomenon ranging from small periodontal defects to large defects following trauma, surgery or congenital malformations. It is imperative to address these defects with utmost care and precision to avoid functional and aesthetic problems. The human oral cavity is a rich source of adult mesenchymal stem cells. Researchers have documented their isolation and studied them extensively for their invitro capacity of hard and soft tissue regeneration. One of the widely studied properties is their osteogenic potential. Bone formation using oral stem cells has shown successful results in numerous animal trials. Some studies have progressed to evaluate their future potential in humans. Highlight This review aimed at discussing the use of human oral stem cells, specifically for bone regeneration in human maxillofacial region. Conclusion Oral stem cells have excellent potential for bone formation and can be successfully used to replace traditionally used bone marrow stem cells. Some sources like stem cells from human exfoliated deciduous teeth (SHED), dental follicle stem cells (DFSC), Stem Cells from Apical Papilla (SCAP), and others need assessment beyond animal models and require human studies for clinical use. More clinical trials of randomized nature are suggested to standardize the clinical procedure and strengthen the claim of oral stem cells as potential replacement of bone marrow counterparts.