Harnessing nature's potential: Alpinia galanga methanolic extract mediated green synthesis of silver nanoparticle, characterization and evaluation of anti-neoplastic activity.

With the advent of nanotechnology, the treatment of cancer is changing from a conventional to a nanoparticle-based approach. Thus, developing nanoparticles to treat cancer is an area of immense importance. We prepared silver nanoparticles (AgNPs) from methanolic extract of Alpinia galanga rhizome and characterized them by UV-Vis spectrophotometry, Fourier transform Infrared (FTIR) spectroscopy, Zetasizer, and Transmission electron Microscopy (TEM). UV-Vis spectrophotometry absorption spectrum showed surface plasmon between 400 and 480 nm. FTIR spectrum analysis implies that various phytochemicals/secondary metabolites are involved in the reduction, caping, and stabilization of AgNPs. The Zetasier result suggests that the particles formed are small in size with a low polydispersity index (PDI), suggesting a narrow range of particle distribution. The TEM image suggests that the particles formed are mostly of spherical morphology with nearly 20-25 nm. Further, the selected area electron diffraction (SAED) image showed five electron diffraction rings, suggesting the polycrystalline nature of the particles. The nanoparticles showed high anticancer efficacy against cervical cancer (SiHa) cell lines. The nanostructures showed dose-dependent inhibition with 40% killing observed at 6.25 µg/mL dose. The study showed an eco-friendly and cost-effective approach to the synthesis of AgNPs and provided insight into the development of antioxidant and anticancer agents.

Clinical significance of SPOP and APC gene alterations in colorectal cancer in Indian population.

Speckle-Type Poz Protein (SPOP) involved in the regulation of proteasome-mediated degradation of several oncoproteins, resulting in cancer initiation and progression. Mutations in Adenomatous Polyposis Coli (APC) gene is reported in most sporadic and hereditary colorectal cancer (CRC). Identifying the cellular changes involved in carcinogenesis when APC is mutated is an important issue that needs attention. The tumor suppressive function of SPOP and APC has long been a major focus in the research field of colorectal cancer. However, the clinical significance of SPOP and APC gene alteration in CRC has not been established to date. Mutational analysis was performed by single-strand conformational polymorphism followed by Sanger sequencing, methylation status by methylation-specific PCR, and protein expression by immunohistochemistry on 142 tumor tissues along with their adjacent non-cancerous specimens. The overall survival (OS) and recurrence free survival (RFS) were estimated by Kaplan-Meier Curve. Mutation rates of APC and SPOP gene were 2.8% and 11.9% while that of promoter hypermethylation were 37% and 47%, respectively. The grade of differentiation and Lymph node metastasis were significantly correlated with APC methylation pattern (p ≤ 0.05). The down regulation of APC was more often seen in colonic cancer compared to rectal cancer (p = 0.07) and more commonly in T3-4 depth of invasion (p = 0.07) and in patients without lymphovascular and perineural invasion (p = 0.007, p = 0.08 respectively). The median overall survival and recurrence free survival (RFS) was 67 & 36 months while 3-yr and 5-yr OS and RFS were 61.1% & 56.4% and 49.2% & 44.8%, respectively. APC promoter methylation had a better overall survival (p = 0.035) while loss of SPOP expression had a worse survival (p = 0.09). Our findings reveal high percentage of SPOP gene mutations in CRC. A significant link is found between promoter hyper methylation and protein expression in all mutant cases of APC and SPOP, suggesting that both genes may be associated in the development of colorectal cancer in people of Indian decent. Hypermethylation of APC gene and loss of SPOP expression have shown an association with disease prognosis and could be further studied looking at its potential role in planning adjuvant treatment in CRC patients.

Mannose-binding lectin gene 2 variant DD (rs 5030737) is associated with susceptibility to COVID-19 infection in the urban population of Patna City (India).

The study aimed to measure plasma levels of Mannose-Binding Lectin (MBL) and MBL-associated serine protease-2 (MASP-2) and their polymorphisms in COVID-19 patients and controls to detect association. As MBL is a protein of immunological importance, it may contribute to the first-line host defence against SARS-CoV-2. MBL initiates the lectin pathway of complement activation with help of MASP-1 and MASP-2. Hence, appropriate serum levels of MBL and MASPs are crucial in getting protection from the disease. The polymorphisms of MBL and MASP genes affect their plasma levels, impacting their protective function and thus may manifest susceptibility, extreme variability in the clinical symptoms and progression of COVID-19 disease. The present study was conducted to find plasma levels and genetic variations in MBL and MASP-2 in COVID-19 patients and controls using PCR-RFLP and ELISA, respectively.The present study was conducted to find plasma levels and genetic variations in MBL and MASP-2 in COVID-19 patients and controls using PCR-RFLP and ELISA, respectively. Our results indicate that median serum levels of MBL and MASP-2 were significantly low in diseased cases but attained normal levels on recovery. Only genotype DD was found to be associated with COVID-19 cases in the urban population of Patna city.

Molecular aspects of ABCB1 and ABCG2 in Gallbladder cancer and its clinical relevance.

The function of ABC transporters in the body is manifold; such as maintenance of homeostasis, effect on multi-drug resistance and their role in tumor initiation & progression. Evidence pointing towards the direct or indirect role of ABC transporter genes in particular; ABCB1 and ABCG2 in cancer genesis is increasing. However, their role in gallbladder cancer is unexplored. Therefore, we investigated the methylation status and expression pattern of ABCB1 and ABCG2in gallbladder carcinogenesis. The methylation and expression study of ABCB1/MDR1 and ABCG2/BCRP was performed in tumour and normal fresh tissue samples collected from 61 histopathologically diagnosed gallbladder cancer patients. The methylation status was analysed by Methylation-Specific PCR and expression was determined by Real-Time PCR and Immunohistochemistry. Hypomethylation of ABCB1 and ABCG2 was found in 44 (72.13%) and 48 (78.6%) cases, respectively. ABCB1 hypomethylation pattern showed association with female patients (p = 0.040) and GradeII tumors (p = 0.036) while, ABCG2 hypomethylation was more frequent in early tumors (T1-T2). The mRNA expression ofABCB1 and ABCG2 was up-regulated in 33 (54.10%) and 41 (67.21%) patients with fold change of 4.7 and 5.5, respectively. The mRNA expression of both genes showed association with Grade II tumours and the increased fold change of ABCG2 was higher in (T1-T2) depth of invasion (p = 0.02) and Stage I-II disease (p = 0.08). The protein expression on IHC was strongly positive for ABCB1/MDR1and ABCG2/BCRP in 32 (52.46%) and 45 (73.77%) patients, respectively. The protein expression in ABCG2 showed association with patients age > 50 years (p = 0.04) and GradeII differentiation (p = 0.07). Interestingly, the hypomethylation of both the genes showed significant correlation with increased expression. ABCB1/MDR1 and ABCG2/BCRP hypomethylation and overexpression could have a potential role in gallbladder cancer tumorigenesis especially in early stages. The epigenetic change might be a plausible factor for altered gene expression of ABCB1 and ABCG2 in gallbladder cancer.

Implication of gut microbes and its metabolites in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer with a significant impact on loss of life. In 2020, nearly 1.9 million new cases and over 9,35,000 deaths were reported. Numerous microbes that are abundant in the human gut benefit host physiology in many ways. Although the underlying mechanism is still unknown, their association appears to be crucial in the beginning and progression of CRC. Diet has a significant impact on the microbial composition and may increase the chance of getting CRC. Increasing evidence points to the gut microbiota as the primary initiator of colonic inflammation, which is connected to the development of colonic tumors. However, it is unclear how the microbiota contributes to the development of CRCs. Patients with CRC have been found to have dysbiosis of the gut microbiota, which can be identified by a decline in commensal bacterial species, such as those that produce butyrate, and a concurrent increase in harmful bacterial populations, such as opportunistic pathogens that produce pro-inflammatory cytokines. We believe that using probiotics or altering the gut microbiota will likely be effective tools in the fight against CRC treatment. PURPOSE: In this review, we revisited the association between gut microbiota and colorectal cancer whether cause or effect. The various factors which influence gut microbiome in patients with CRC and possible mechanism in relation with development of CRC. CONCLUSION: The clinical significance of the intestinal microbiota may aid in the prevention and management of CRC.

Evaluation of C4b as an adjunct marker in symptomatic RT-PCR negative Covid-19 cases.

Introduction: Detecting low viral load has been a challenge in this pandemic, which has led to its escalated transmission. Complement activation has been implicated in pathogenesis of Covid-19 infection. Thus, evaluation of complement activation in suspected Covid-19 infection may help to detect infection and limit false negative cases thus limiting transmission of infection. We speculate that measuring C4b, produced from an activated complement system due to the presence of Covid-19 may help in its detection, even when the viral titers are low. Methods: Plasma C4b levels of symptomatic RT-PCR positive patients (cases, n = 40); symptomatic RT-PCR negative patients (n = 35) and asymptomatic RT-PCR negative controls (n = 40) were evaluated. Plasma C5b-9, IL-6, D-dimer and C1-Inhibitor (C1-INH) were also measured in cases and controls. ELISA kits were used for all measurements. Statistical analyses were carried out using Stata, version 12 (Stata Corp., Texas, USA). Results: C4b levels were found to be significantly increased in RT-PCR positive patients as compared to asymptomatic RT-PCR negative controls. RT-PCR negative but symptomatic patients still showed increased C4b levels. The significantly higher levels of C4b in cases with a cut-off value of ≥ 116 ng/ml with optimum sensitivity and specificity of 80% and 52% respectively is indicative of its possible use as an adjunct marker. Increased levels of D-dimer, IL6, along with decreased levels of C1-INH were found in cases compared to controls. Whereas, C5b-9 levels were not significantly raised in cases. Conclusions: The results of our study suggests that plasma C4b may help to detect infection in false negative cases of RT-PCR that escape detection owing to low viral load. However, to confirm it a large-scale study is needed. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01033-z.

A non-invasive miRNA-based approach in early diagnosis and therapeutics of oral cancer.

Oral or mouth cancer is the 16th most common form of cancer among the world's topmost malignancies. Healthy lifestyle and control of known risk factors can reduce its incidences further. Patients succumb to oral cancer when diagnosed late and lack timely access to tertiary care. Molecular biomarkers might help in early detection of oral cancer. Recently, researchers have identified numerous microRNAs which play a crucial role in promoting and suppressing oral cancers. miRNAs are short non-coding RNA molecules (18-22 nucleotides) that play a pivotal role in regulating gene expression. Understanding the miRNA interplays in oral cancers could augment the development of potential diagnostic, prognostic, and therapeutic tools. Liquid biopsy- a non-invasive approach that has been used lately, allows the determination of miRNAs in biological fluids that play essential roles in tumor suppression and cancer promotion. Herein, we summarize an update on the role of miRNAs in the diagnosis and treatment of oral cancer.

Diagnostic and prognostic biomarkers in colorectal cancer and the potential role of exosomes in drug delivery.

Colorectal cancer (CRC) is the third most common cancer with the second most frequent cause of death worldwide. One fourth to one fifth of the CRC cases are detected at advance stage. Early detection of colorectal cancer might help in decreasing mortality and morbidity worldwide. CRC being a heterogeneous disease, new non-invasive approaches are needed to complement and improve the screening and management of CRC. Reliable and early detectable biomarkers would improve diagnosis, prognosis, therapeutic responses, and will enable the prediction of drug response and recurrence risk. Over the past decades molecular research has demonstrated the potentials of CTCs, ctDNAs, circulating mRNAs, ncRNAs, and exosomes as tumor biomarkers. Non-invasive screening approaches using fecal samples for identification of altered gut microbes in CRC is also gaining attention. Exosomes can be potential candidates that can be employed in the drug delivery system. Further, the integration of in vitro, in vivo and in silico models that involve CRC biomarkers will help to understand the interactions occurring at the cellular level. This review summarizes recent update on CRC biomarkers and their application along with the nanoparticles followed by the application of organoid culture in CRC.

S1P signaling, its interactions and cross-talks with other partners and therapeutic importance in colorectal cancer.

Sphingosine-1-Phosphate (S1P) plays an important role in normal physiology, inflammation, initiation and progression of cancer. Deregulation of S1P signaling causes aberrant proliferation, affects survival, leads to angiogenesis and metastasis. Sphingolipid rheostat is crucial for cellular homeostasis. Discrepancy in sphingolipid metabolism is linked to cancer and drug insensitivity. Owing to these diverse functions and being a potent mediator of tumor growth, S1P signaling might be a suitable candidate for anti-tumor therapy or combination therapy. In this review, with a focus on colorectal cancer we have summarized the interacting partners of S1P signaling pathway, its therapeutic approaches along with the contribution of S1P signaling to various cancer hallmarks.

Cross-talk between next generation sequencing methodologies to identify genomic signatures of esophageal cancer.

The asymptomatic behaviour of esophageal cancerous cells at early stages develops advanced clinical presentation of the disease, resulting in poor prognosis and curbed intervention of therapeutic modalities. The endeavours to detect diagnostic and prognostic markers have been proven futile at the clinical platform. While several biomarkers have been investigated, including CYFRA 21-1, carcinoembryonic antigen and squamous cell carcinoma antigen, their sensitivity has not proved consistently satisfactory across the various stages of esophageal cancer. Hence, there is an impending requirement of biomarkers for early diagnosis and better prognosis. In the recent past, next generation sequencing (NGS) tool has emerged as an important tool to highlight the hallmarks of esophageal cancer (EC). This review summarizes the changes/mutations occurred in tumor cells during carcinogenesis and addresses the contribution of NGS techniques, viz. whole genome sequencing (WGS), RNA-Sequencing and Exome sequencing (ES), in EC. Additionally, this review highlights the connection between the findings from these techniques. An effort has been made to emphasize the genes affected and involved signaling pathway in EC. Further, investigations of these mutated genes would not only shed light on the relevant genes to be studied but also help in the better management and cure through personalized therapy.

Elucidation of Epigenetic Landscape in Coronary Artery Disease: A Review on Basic Concept to Personalized Medicine.

Despite extensive clinical research and management protocols applied in the field of coronary artery diseases (CAD), it still holds the number 1 position in mortality worldwide. This indicates that we need to work on precision medicine to discover the diagnostic, therapeutic, and prognostic targets to improve the outcome of CAD. In precision medicine, epigenetic changes play a vital role in disease onset and progression. Epigenetics is the study of heritable changes that do not affect the alterations of DNA sequence in the genome. It comprises various covalent modifications that occur in DNA or histone proteins affecting the spatial arrangement of the DNA and histones. These multiple modifications include DNA/histone methylation, acetylation, phosphorylation, and SUMOylation. Besides these covalent modifications, non-coding RNAs-viz. miRNA, lncRNA, and circRNA are also involved in epigenetics. Smoking, alcohol, diet, environmental pollutants, obesity, and lifestyle are some of the prime factors affecting epigenetic alterations. Novel molecular techniques such as next-generation sequencing, chromatin immunoprecipitation, and mass spectrometry have been developed to identify important cross points in the epigenetic web in relation to various diseases. The studies regarding exploration of epigenetics, have led researchers to identify multiple diagnostic markers and therapeutic targets that are being used in different disease diagnosis and management. Here in this review, we will discuss various ground-breaking contributions of past and recent studies in the epigenetic field in concert with coronary artery diseases. Future prospects of epigenetics and its implication in CAD personalized medicine will also be discussed in brief.