IL-18 Gene Promoter Polymorphisms are Involved in Periodontal Disease: A Meta-Analysis.

Microbial plaque that builds up in the gingival crevice area causes inflammation and leads to periodontal disease. Previous research has shown an association between interleukins with periodontitis. The association between interleukin-18 (IL-18) gene polymorphism and periodontitis risk was studied extensively, but the results are contradictory. The aim of this study is to find the association of two IL-18 promoter variants namely -607 C > A (rs1946518) and -137 G > C (rs187238), and the risk of chronic and aggressive periodontal disease by meta-analysis. The databases of PubMed, Medline, Web of Science, and Google Scholar were all explored to find the appropriate studies. The MetaGenyo software was used to calculate each analysis. Outcomes of the pooled analyses revealed significantly elevated risk for periodontitis for both polymorphisms. There is no significant heterogeneity between studies. No significant publication bias was observed. This meta-analysis provided the evidence of a link between IL-18 gene polymorphism in periodontitis.

Role of CD4+ T Cells in Parkinson's Disease.

Parkinson's disease (PD) is a progressive condition that affects both the central nervous system and other body parts that are controlled by the nervous system. PD is characterized by brain dopaminergic neurons loss and, at present, there are only symptomatic treatments available to alleviate the effects of the disease. With extensive research, new insights have led to defining PD as a multi-system disorder with immune dysfunction playing a dominant part in the disease pathogenesis as well as its progression. Neuroinflammation in PD leads to neurodegeneration, which is, in turn, regulated by the peripheral adaptive immunity, with CD4+ T cells being a significant player. Patients with PD have diverse CD4+ T cell phenotypes and functional profiles. These phenotypes vary, from being proinflammatory (Th1 and Th17) to anti-inflammatory (Th2 and Tregs). This report focuses on reviewing the expression of CD4+ T cells in PD and its role in the prognosis and treatment of PD.

Regulatory T cells: Their role in triple-negative breast cancer progression and metastasis.

Triple-negative breast cancer (TNBC) is an aggressive and immunogenic subtype of breast cancer. This tumorigenicity is independent of hormonal or HER2 pathways because of a lack of respective receptor expression. TNBC is extremely prone to drug resistance and early recurrence because of T-regulatory cell (Treg) infiltration into the tumor microenvironment (TME) in addition to other mechanisms like genomic instability. Tumor-infiltrating Tregs interact with both tumor and stromal cells as well as extracellular matrix components in the TME and induce an immune-suppressive phenotype. Hence, treatment of TNBC with conventional therapies remains challenging. Understanding the protective mechanism of Tregs in shielding TNBC from antitumor immune responses in the TME will pave the way for developing novel, immune-based therapeutics. The current review focuses on the role of tumor-infiltrating Tregs in tumor progression and metabolic reprogramming of the TME. The authors have extended their focus to oncotargeting Treg-mediated immune suppression in breast cancer. Because of its potential role in the TME, modulating Treg activity may provide a novel strategic intervention to combat TNBC. Both under laboratory conditions and in clinical trials, currently available anticancer drugs and natural therapeutics as potential agents for targeting Tregs are explored.

Targeting T regulatory cells: Their role in colorectal carcinoma progression and current clinical trials.

Colorectal cancer (CRC) is classified as the third leading cancer globally and one of the major causes of morbidity and mortality around the world. The interaction of the immune system with the cancer cells plays a vital role in CRC progression. Regulatory T cells (Tregs) are a form of T cells, which regulate and suppress unwanted activation of the immune system and play a major role in preventing autoimmune diseases. Tregs exhibit a significant role in immune modulation during CRC progression through accumulation in the tumor microenvironment (TME) and suppression of immunity against tumor specific antigens promoting tumor progression. The role of Tregs in CRC progression and its interaction with other immune cells within CRC TME and current clinical trials were reviewed in this paper.

Matrix metalloproteinases: their functional role in lung cancer.

Lung malignancy is the foremost cause of cancer-related deaths globally and is frequently related to long-term tobacco smoking. Recent studies reveal that the expression of matrix metalloproteinases (MMPs) is extremely high in lung tumors compared with non-malignant lung tissue. MMPs are zinc-dependent proteases and are involved in the degradation of extracellular matrix (ECM). Several investigations have shown that MMPs manipulate the activity of non-ECM molecules, including cytokines, growth factors and receptors that control the tumor microenvironment. In this review, we have summarized and critically reviewed the published works on the role of MMPs in non-small-cell lung cancer. We have also explored the structure of MMPs, their various types and roles in lung cancer metastasis including invasion, migration and angiogenesis.

Resveratrol: biology, metabolism, and detrimental role on the tumor microenvironment of colorectal cancer.

A substantial increase in colorectal cancer (CRC)-associated fatalities can be attributed to tumor recurrence and multidrug resistance. Traditional treatment options, including radio- and chemotherapy, also exhibit adverse side effects. Ancient treatment strategies that include phytochemicals like resveratrol are now widely encouraged as an alternative therapeutic option. Resveratrol is the natural polyphenolic stilbene in vegetables and fruits like grapes and apples. It inhibits CRC progression via targeting dysregulated cancer-promoting pathways, including PI3K/Akt/Kras, targeting transcription factors like NF-κB and STAT3, and an immunosuppressive tumor microenvironment. In addition, combination therapies for cancer include resveratrol as an adjuvant to decrease multidrug resistance that develops in CRC cells. The current review discusses the biology of resveratrol and explores different mechanisms of action of resveratrol in inhibiting CRC progression. Further, the detrimental role of resveratrol on the immunosuppressive tumor microenvironment of CRC has been discussed. This review illustrates clinical trials on resveratrol in different cancers, including resveratrol analogs, and their efficiency in promoting CRC inhibition.

Cancer Stem Cells and Circulatory Tumor Cells Promote Breast Cancer Metastasis.

Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC.

Biomarkers of Oxidative Stress Tethered to Cardiovascular Diseases.

Cardiovascular disease (CVD) is a broad term that incorporated a group of conditions that affect the blood vessels and the heart. CVD is a foremost cause of fatalities around the world. Multiple pathophysiological mechanisms are involved in CVD; however, oxidative stress plays a vital role in generating reactive oxygen species (ROS). Oxidative stress occurs when the concentration of oxidants exceeds the potency of antioxidants within the body while producing reactive nitrogen species (RNS). ROS generated by oxidative stress disrupts cell signaling, DNA damage, lipids, and proteins, thereby resulting in inflammation and apoptosis. Mitochondria is the primary source of ROS production within cells. Increased ROS production reduces nitric oxide (NO) bioavailability, which elevates vasoconstriction within the arteries and contributes to the development of hypertension. ROS production has also been linked to the development of atherosclerotic plaque. Antioxidants can decrease oxidative stress in the body; however, various therapeutic drugs have been designed to treat oxidative stress damage due to CVD. The present review provides a detailed narrative of the oxidative stress and ROS generation with a primary focus on the oxidative stress biomarker and its association with CVD. We have also discussed the complex relationship between inflammation and endothelial dysfunction in CVD as well as oxidative stress-induced obesity in CVD. Finally, we discussed the role of antioxidants in reducing oxidative stress in CVD.

A Review on Hematopoietic Stem Cell Treatment for Epilepsy.

Epilepsy responds to pharmacotherapy in its initial stages. The response of some forms of epilepsy, like the refractory epilepsy, is extremely low. Surgical management of epilepsy is associated with complications, which necessitates the search for novel and modern strategies for the treatment of epilepsy. Neuroprotection and neuronal regeneration are the major targets that must be accomplished by the new strategies. Hematopoietic Stem Cell (HSCs) therapy for epilepsy has shown promising results in pre-clinical studies with marginal clinical effects. This review explores the characteristics, mechanism of action, and clinical significance of HSCs therapy for the treatment of epilepsy.

Tumor Necrosis Factor-Alpha Gene Promoter (TNF-α G-308A) Polymorphisms Increase the Risk of Hepatocellular Carcinoma in Asians: A Meta-Analysis.

Hepatocellular carcinoma (HCC) is one of the most common primary hepatic tumors, and it is ranked as the third most common cause of cancer-linked deaths. Although the precise etiology of HCC is unknown, inflammation has been considered the foremost cause of HCC. Previous studies indicated that tumor necrosis factor-alpha (TNF-α) is associated with increased risk of HCC, but the results are conflicting. In the present study, we assessed the correlation between TNF-α G-308A polymorphism as well as HCC risk via a meta-analysis. We searched databases such as PubMed, EMBASE, and Web of Science for articles related to this subject. To evaluate the correlation between TNF-α G-308A polymorphism and HCC, the odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Between-study heterogeneity was assessed using Cochrane Q test and I2 statistics. To assess the robustness of data, sensitivity analysis, publication bias, and subgroup analysis were conducted. Approximately 30 articles with 4,753 cases of HCC and 6,667 controls were included for the meta-analysis. Overall, the TNF-α G-308A polymorphism notably correlated with increased risk of HCC in the dominant model (OR = 1.41, 95% CI: 1.02-1.94, P = 0.036). Furthermore, a subgroup investigation showed significant correlation between TNF-α G-308A polymorphisms and HCC risk only in Asian populations (dominant model OR = 1.55, 95% CI: 1.05-2.23, P = 0.025). Studies in ethnic groups showed significant heterogeneity (I2 > 50%). Funnel plot and Eggers p values did not reveal publication bias. The present meta-analysis suggested that TNF-α G-308A polymorphisms are correlated with an elevated risk of HCC in Asian populations.

Breast Tumor Microenvironment: Emerging target of therapeutic phytochemicals.

Triple negative breast cancer (TNBC) is the most aggressive and challenging form of breast cancers. Tumor microenvironment (TME) of TNBC is associated with induction of metastasis, immune system suppression, escaping immune detection and drug resistance. TME is highly complex and heterogeneous, consists of tumor cells, stromal cells and immune cells. The rapid expansion of tumors induce hypoxia, which concerns the reprogramming of TME components. The reciprocal communication of tumor cells and TME cells predisposes cancer cells to metastasis by modulation of developmental pathways, Wnt, notch, hedgehog and their related mechanisms in TME. Dietary phytochemicals are non-toxic and associated with various human health benefits and remarkable spectrum of biological activities. The phytochemicals serve as vital resources for drug discovery and also as a source for breast cancer therapy. The novel properties of dietary phytochemicals propose platform for modulation of tumor signaling, overcoming drug resistance, and targeting TME. Therefore, TME could serve as promising target for the treatment of TNBC. This review presents current status and implications of experimentally evaluated therapeutic phytochemicals as potential targeting agents of TME, potential nanosystems for targeted delivery of phytochemicals and their current challenges and future implications in TNBC treatment. The dietary phytochemicals especially curcumin with significant delivery system could prevent TNBC development as it is considered safe and well tolerated in phase II clinical trials.

Colorectal Cancer Biology, Diagnosis, and Therapeutic Approaches.

Colorectal cancer (CRC) is the second most diagnosed disease worldwide. It is the fourth leading cause of cancer related mortalities. Higher probability for the occurrence of CRC is due to western lifestyle, age, and personal history of chronic diseases. The development of CRC is a multistep process that includes a sequence of genetic, histological, and morphological alterations that accumulate over time. Furthermore, depending on the origin of mutations, CRC can be classified as familial, sporadic, and inherited, based on which a therapeutic plan is created for a CRC patient. These mutations cause chromosomal alterations and translocations in genes that lead to microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and chromosomal instability (CIN). The mutations affect dysregulation of various pathways that are responsible for cancer progression. They include the PI3K/Akt, Wnt, TP53, and MAPK pathways. Mutated genes, such as KRAS, PTEN, SMAD4, BRAF, and PTEN, are employed as predictive biomarkers for early diagnosis. The conventional therapies of CRC start with surgical resection followed by adjuvant therapies, such as radiotherapy and chemotherapy. Researchers are now developing therapies that combine triplet drugs to overcome the hurdle of multidrug resistance (MDR). The combination of chemotherapy with immunotherapy to target the dysregulated proteins, such as EGFR and VEGFR is found efficient for advanced mCRC therapy. Researchers are now developing personalized medicines by detecting and validating key biomarkers to understand the mechanism of MDR and toxicity. In this review, we address genetic alterations, current data on biomarkers, and novel therapeutic approaches for the treatment of CRC.

Current updates on the European and WHO registered clinical trials of coronavirus disease 2019 (COVID-19).

Coronavirus disease 2019 (COVID-19) is a major public health concern currently. To date, there are no approved antiviral drugs or vaccines against this transmissible disease. This report sheds light on available information for a better understanding of clinical trials and pharmacotherapy related to COVID-19. MEDLINE, PubMed, EMBASE, Scopus databases, Web of Science, WHO, and EU clinical trial sites were used to perform comparative analysis. Information was collected on the use of therapeutic agents for human therapy in patients with COVID-19 up to May 2020. We have extracted data from 60 clinical trials. Amongst these trials, 34 were from the European Union database of clinical trials and 26 from the National Institute of Health. The data selection procedure includes active, completed, and recruitment in progress status. Most of the clinical trials are ongoing and hence, there is a lack of precise results for the treatment.There is a lack of high-quality clinical evidence. The protocol to be developed requires large randomized clinical trials with a combination of available drugs and prospective therapies. We propose the usage of a large number of cases and different statistical analyses to conduct systematic clinical trials. This could provide comprehensive information about the clinical trial and potential therapeutic progress.

DNA Fingerprint Technology: Its Application in Detecting Pancreatic Cancer.

Pancreatic cancer (PC) is one of the most lethal forms of cancers, ranking as the third highest cause of malignancies and fatalities. Approximately 88% of patients diagnosed with PC are older than 55 yr. Due to PC's vague symptoms, patients typically visit their doctor only when they experience symptoms of extreme pain and/or after their bile ducts have blocked. This produces symptoms including darkly colored urine, jaundice, and light-colored stools. At this point in the progression of the disease, the tumor has already metastasized. Early detection of PC is critical and justifies the need for innovative techniques to efficiently aid in this process. Current research involves screening different aspects of the disease, imaging techniques, and evaluating blood, urine, cell, and saliva biomarkers. We propose that forensic DNA fingerprinting can be used to establish the role of genetics in PC, and we describe disease inheritance patterns so that relatives can understand the likelihood of developing this lethal malignancy.

5-Lipoxygenase: Its involvement in gastrointestinal malignancies.

Lipoxygenases (LOXs) are dioxygenases that catalyze the peroxidation of linoleic acid (LA) or arachidonic acid (AA), in the presence of molecular oxygen. The existence of inflammatory component in the tumor microenvironment intimately links the LOXs to gastrointestinal (GI) cancer progression. Amongst the six-different human LOX-isoforms, 5-LOX is the most vital enzyme for leukotriene (LT) biosynthesis, which is the main inflammation intermediaries. As recent investigations have shown the association of 5-LOX with tumor metastasis, there has also been significant progress in discovering the function of 5-LOX pathway in GI cancer. Studies on GI cancer cells using the pharmacological drugs targeting 5-LOX pathway have shown antiproliferative and proapoptotic effects. Pharmacogenetic discoveries in other diseases have revealed strong heritable basis for the leukotriene pathway, which helps in exploring the mechanistic source of genetic alteration within the leukotriene pathway and offer insights into GI cancer pathogenesis and future prospects for treatment and prevention. This review recapitulates the current research status of 5-LOX activity in GI malignancies.

Targeting autophagy in gastrointestinal malignancy by using nanomaterials as drug delivery systems.

Autophagy is a conserved catabolic process involving large protein degradation by a ubiquitous autophagosomic signaling pathway, which is essential for cellular homeostasis. It is triggered by environmental factors such as stress, lack of nutrients, inflammation, and eliminating intracellular pathogens. Although the mechanisms underlying autophagy are still unclear, increasing evidence illuminates the magnitude of autophagy in a wide range of physiological processes and human diseases. Simultaneously, research community has focused on the triggering of autophagy by the internalization of engineered nanomaterials, which indicates a new line of revolution in cancer cure. However, most studies on nanoparticle-induced autophagy focus on brain, breast, and cervical cancers; limited reports are available on gastrointestinal (GI) cancers. Therefore, the aim of this mini review is to discuss in detail the role of autophagy in GI malignancy and the status of research on nanoparticle-induced autophagy.

Role of hypoxia-inducible factors (HIF) in the maintenance of stemness and malignancy of colorectal cancer.

Hypoxia is a condition of insufficient tissue oxygenation, which is observed during normal development as well as tumorigenesis and its response at the cellular level is primarily mediated through hypoxia inducible factors (HIFs). HIFs have a significant role in the maintenance of stemness in both stem cells as well as in cancer stem cells (CSC) by acting as transcription factors. The CSCs are proposed to be the driving force of colon tumorigenesis and malignancy. These HIFs play a significant role in a wide range of diseases including colon cancer. HIF's signaling functions with stemness, and maintaining Wnt/ß-catenin signaling pathways. Due to HIFs functional significance in stemness maintenance in malignancy, targeting HIFs might provide a new approach for development of new therapy for colon cancer. In this review, we will be briefing on the colon and its stem cells, various molecular signaling pathways involved in stemness preservation, and the role hypoxia and its HIFs in the maintenance of stemness in colon stem cells and colon cancer stem cells.

Epigenetic effects of inhibition of heat shock protein 90 (HSP90) in human pancreatic and colon cancer.

Silencing of tumor suppressor and DNA repair genes through methylation plays a role in cancer development, growth and response to therapy in colorectal and pancreatic cancers. Heat shock protein 90 (HSP90) regulates transcription of DNA methyltransferase enzymes (DNMT). In addition, DNMTs are client proteins of HSP90. The aim of this study is to evaluate the effects of HSP90 inhibition on DNA methylation in colorectal and pancreatic cancer cell lines. Our data shows that inhibition of HSP90 using ganetespib resulted in downregulation of mRNA and protein expression of DNMT1, DNMT3A, and DNMT3B in HT-29 and MIA PaCa-2 cell lines. This in turn was associated with a drop in the fraction of methylated cytosine residues and re-expression of silenced genes including MLH-1, P16 and SPARC. These effects were validated in HT-29 tumors implanted subcutaneously in mice following in vivo administration of ganetespib. This work demonstrates the effectiveness of ganetespib, an HSP90 inhibitor in modulating DNA methylation through downregulation of DNMT expression.

Adiponectin: Its role in obesity-associated colon and prostate cancers.

Adipose tissue synthesizes many proteins and hormones collectively called adipokines, which are linked to a number of diseases, including cancer. Low levels of adiponectin are reported to be a risk factor for obesity-related cancers including colorectal and prostate cancers. Accordingly, obesity/lifestyle-related diseases, including certain cancers, may be treated by developing drugs that act specifically on adiponectin levels in circulation. Adiponectin may also serve as a clinical biomarker in obesity-related diseases. Adiponectin-based therapies are known to inhibit cancer advancement and thus may provide a therapeutic approach to delay cancer progression. Better understanding of the function of adiponectin is of great significance in the fight against cancer. This timely review is concentrated on the role of adiponectin and the impact of obesity on the development of cancers, especially colorectal and prostate cancers.