: Tumor associated macrophages (TAMs), located in the tumor microenvironment (TME), play a significant role in cancer cell survival and progression. TAMs have been involved in producing immuno-suppressive TME in the tumor by generating inflammatory mediators, growth factors, cytokines, chemokines, etc. TAMs can influence the angiogenesis, metastatic behavior of tumor cells (TCs) and cause multidrug resistance. TAMs within the TME can enhance cancer cell metastasis and are stromal and perivascular. The angiogenesis is promoted at the hypoxia, and the avascular zones of TME. Differentiation states of TAMs are considered ‘plastic’ as they exhibit temporal expression of one or several phenotypes depending on local cues. Emerging cancer research depicted the epigenetic regulation of macrophage polarization (both M1s, M2s) and their potential implications to develop pharmacologic modulators and microRNAs to act as molecular switches and even to serve as targeted therapies to inhibit tumor growth. In the present article, the role of TAMs in tumor progression, angiogenesis and metastasis was discussed. In addition, key signaling cascades regulated by TAMs, which have a role in chemoresistance, were also discussed. Currently, novel pleiotropic properties of various anticancer phytomedicines are gaining importance as they assist in overcoming TAMs-induced chemoresistance. Moreover, these phytomedicines are being tested as ‘adjunct therapeutics’ along with chemotherapeutic agents, anti-angiogenic molecules, anti-metastatic compounds, and other immune-checkpoint blockers against tumor metastasis/angiogenesis. Hence, a brief note on natural products targeting TAMs was provided. In summary, this review would benefit pharmacologists and medical professionals to develop therapies to target TAMs using multi-OMICs approaches, including genomics, epigenomics, transcriptomics, and proteomics.

Recent evidence relating to the impact of COVID-19 on people with diabetes is limited but continues to emerge. COVID-19 pneumonia is a newly identified illness spreading rapidly throughout the world and causes many disabilities and fatal deaths. Over the ensuing 2 years, the indirect effects of the pandemic on healthcare delivery have become prominent, along with the lingering effects of the virus on those directly infected. Diabetes is a commonly identified risk factor that contributes not only to the severity and mortality of COVID-19 patients, but also to the associated complications, including acute respiratory distress syndrome (ARDS) and multi-organ failure. Diabetic patients are highly affected due to increased viral entry into the cells and decreased immunity. Several hypotheses to explain the increased incidence and severity of COVID-19 infection in people with diabetes have been proposed and explained in detail recently. On the other hand, 20–50% of COVID-19 patients reported new-onset hyperglycemia without diabetes and new-onset diabetes, suggesting the two-way interactions between COVID-19 and diabetes. A systematic review is required to confirm diabetes as a complication in those patients diagnosed with COVID-19. Diabetes and diabetes-related complications in COVID-19 patients are primarily due to the acute illness caused during the SARS-CoV-2 infection followed by the release of glucocorticoids, catecholamines, and pro-inflammatory cytokines, which have been shown to drive hyperglycemia positively. This review provides brief insights into the potential mechanisms linking COVID-19 and diabetes, and presents clinical management recommendations for better handling of the disease.

Vaccines against severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2) infection, which causes coronavirus disease–19 (COVID-19) in humans, have been developed and are being tested for safety and efficacy. We conducted the cross-sectional prospective cohort study on 820 patients who were positive for SARS-CoV-2 and were admitted to Princess Krishnajammanni trauma care centre (PKTCC), Mysore, which was converted to a designated COVID hospital between April 2021 to July 2021. After obtaining the informed consent, RT-PCR report, vaccination certificate and patient history, patients were classified according to their vaccination status. Results from the study showed decreases in serum ferritin levels, clinical symptoms, improvement in oxygen saturation, early recovery in patients having diabetes and hypertension, and a substantial reduction in the overall duration of hospital stay in vaccinated patients compared to unvaccinated patients. Further, fully vaccinated patients showed better outcomes compared to single dose vaccinated and nonvaccinated patients. Taken together, our findings reaffirm the vaccine’s effectiveness in reducing case fatality and promoting faster recovery compared to nonvaccinated patients. Efforts to increase the number of immunized subjects in the community help to achieve herd immunity and offer protection against the severity of COVID-19 and associated complications while minimizing the public health and economic burden.

The incidence and death toll due to SARS-CoV-2 infection varied time-to-time; and depended on several factors, including severity (viral load), immune status, age, gender, vaccination status, and presence of comorbidities. The RNA genome of SARS-CoV-2 has mutated and produced several variants, which were classified by the SARS-CoV-2 Interagency Group (SIG) into four major categories. The first category; “Variant Being Monitored (VBM)”, consists of Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Epsilon (B.1.427, B.1.429), Eta (B.1.525), Iota (B.1.526), Kappa (B.1.617.1), Mu (B.1.621), and Zeta (P.2); the second category; “Variants of Concern” consists of Omicron (B.1.1.529). The third and fourth categories include “Variants of Interest (VOI)”, and “Variants of High Consequence (VOHC)”, respectively, and contain no variants classified currently under these categories. The surge in VBM and VOC poses a significant threat to public health globally as they exhibit altered virulence, transmissibility, diagnostic or therapeutic escape, and the ability to evade the host immune response. Studies have shown that certain mutations increase the infectivity and pathogenicity of the virus as demonstrated in the case of SARS-CoV-2, the Omicron variant. It is reported that the Omicron variant has >60 mutations with at least 30 mutations in the Spike protein (“S” protein) and 15 mutations in the receptor-binding domain (RBD), resulting in rapid attachment to target cells and immune evasion. The spread of VBM and VOCs has affected the actual protective efficacy of the first-generation vaccines (ChAdOx1, Ad26.COV2.S, NVX-CoV2373, BNT162b2). Currently, the data on the effectiveness of existing vaccines against newer variants of SARS-CoV-2 are very scanty; hence additional studies are immediately warranted. To this end, recent studies have initiated investigations to elucidate the structural features of crucial proteins of SARS-CoV-2 variants and their involvement in pathogenesis. In addition, intense research is in progress to develop better preventive and therapeutic strategies to halt the spread of COVID-19 caused by variants. This review summarizes the structure and life cycle of SARS-CoV-2, provides background information on several variants of SARS-CoV-2 and mutations associated with these variants, and reviews recent studies on the safety and efficacy of major vaccines/vaccine candidates approved against SARS-CoV-2, and its variants.

AimsTo explore the hepatoprotective role of quercetin and its novel molecular mechanism of action on breast cancer associated hepatic inflammation and fibrosis via Vitamin D receptor (VDR).Main methodsWe used Ehrlich Ascites Carcinoma (mouse mammary carcinoma) model for our in-vivo experiments and human breast cancer cell lines for in-vitro assays. We inoculated 1.5 × 106 Ehrlich ascites carcinoma cells into female Swiss albino mice. Quercetin (50 mg/kg) was administered intraperitoneally for 15 days. Liver enzymes activity was determined using a spectrophotometric assay. The hallmarks of inflammation and fibrosis were determined using Immunohistochemistry. The effect of quercetin on tumor formation was elucidated using human breast cancer cell lines and chick chorioallantoic membrane assay. Docking study was performed to explore the binding mode of quercetin with VDR.Key findingsIn EAC tumor-bearing mice, cell numbers, tumor volume, body weight and liver weight were dramatically increased, while they significantly decreased in mice treated with quercetin. Additionally, the peritoneal neo-angiogenesis was also significantly suppressed in the quercetin-treated mice, compared to the control. In addition, quercetin treated EAC tumor bearing mice had lower levels of liver enzymes, decreased hepatic inflammation and fibrosis compared with EAC tumor bearing mice. Docking study confirmed VDR-quercetin interaction. Furthermore, in-vitro assays and chick chorioallantoic membrane assay revealed the Vitamin D mimicking effect of quercetin.SignificanceDietary flavonoid, quercetin could act as a promising therapeutic drug to suppress the breast cancer induced tumor angiogenesis, hepatic inflammation, and fibrosis possibly via activation of VDR.