A Comprehensive Review of Cancer Drug-Induced Cardiotoxicity in Blood Cancer Patients: Current Perspectives and Therapeutic Strategies.

OPINION STATEMENT: Cardiotoxicity has emerged as a serious outcome catalyzed by various therapeutic targets in the field of cancer treatment, which includes chemotherapy, radiation, and targeted therapies. The growing significance of cancer drug-induced cardiotoxicity (CDIC) and radiation-induced cardiotoxicity (CRIC) necessitates immediate attention. This article intricately unveils how cancer treatments cause cardiotoxicity, which is exacerbated by patient-specific risks. In particular, drugs like anthracyclines, alkylating agents, and tyrosine kinase inhibitors pose a risk, along with factors such as hypertension and diabetes. Mechanistic insights into oxidative stress and topoisomerase-II-B inhibition are crucial, while cardiac biomarkers show early damage. Timely intervention and prompt treatment, especially with specific agents like dexrazoxane and beta-blockers, are pivotal in the proactive management of CDIC.

Orchestral role of lipid metabolic reprogramming in T-cell malignancy.

The immune function of normal T cells partially depends on the maneuvering of lipid metabolism through various stages and subsets. Interestingly, T-cell malignancies also reprogram their lipid metabolism to fulfill bioenergetic demand for rapid division. The rewiring of lipid metabolism in T-cell malignancies not only provides survival benefits but also contributes to their stemness, invasion, metastasis, and angiogenesis. Owing to distinctive lipid metabolic programming in T-cell cancer, quantitative, qualitative, and spatial enrichment of specific lipid molecules occur. The formation of lipid rafts rich in cholesterol confers physical strength and sustains survival signals. The accumulation of lipids through de novo synthesis and uptake of free lipids contribute to the bioenergetic reserve required for robust demand during migration and metastasis. Lipid storage in cells leads to the formation of specialized structures known as lipid droplets. The inimitable changes in fatty acid synthesis (FAS) and fatty acid oxidation (FAO) are in dynamic balance in T-cell malignancies. FAO fuels the molecular pumps causing chemoresistance, while FAS offers structural and signaling lipids for rapid division. Lipid metabolism in T-cell cancer provides molecules having immunosuppressive abilities. Moreover, the distinctive composition of membrane lipids has implications for immune evasion by malignant cells of T-cell origin. Lipid droplets and lipid rafts are contributors to maintaining hallmarks of cancer in malignancies of T cells. In preclinical settings, molecular targeting of lipid metabolism in T-cell cancer potentiates the antitumor immunity and chemotherapeutic response. Thus, the direct and adjunct benefit of lipid metabolic targeting is expected to improve the clinical management of T-cell malignancies.

Counteracting Action of Curcumin on High Glucose-Induced Chemoresistance in Hepatic Carcinoma Cells.

Along with direct anticancer activity, curcumin hinders the onset of chemoresistance. Among many, high glucose condition is a key driving factor for chemoresistance. However, the ability of curcumin remains unexplored against high glucose-induced chemoresistance. Moreover, chemoresistance is major hindrance in effective clinical management of liver cancer. Using hepatic carcinoma HepG2 cells, the present investigation demonstrates that high glucose induces chemoresistance, which is averted by the simultaneous presence of curcumin. Curcumin obviated the hyperglycemia-induced modulations like elevated glucose consumption, lactate production, and extracellular acidification, and diminished nitric oxide and reactive oxygen species (ROS) production. Modulated molecular regulators are suggested to play a crucial role as curcumin pretreatment also prevented the onset of chemoresistance by high glucose. High glucose instigated suppression in the intracellular accumulation of anticancer drug doxorubicin and drug-induced chromatin compactness along with declined expression of drug efflux pump MDR-1 and transcription factors and signal transducers governing the survival, aggressiveness, and apoptotic cell death (p53, HIF-1α, mTOR, MYC, STAT3). Curcumin alleviated the suppression of drug retention and nuclear condensation along with hindering the high glucose-induced alterations in transcription factors and signal transducers. High glucose-driven resistance in cancer cells was associated with elevated expression of metabolic enzymes HKII, PFK1, GAPDH, PKM2, LDH-A, IDH3A, and FASN. Metabolite transporters and receptors (GLUT-1, MCT-1, MCT-4, and HCAR-1) were also found upregulated in high glucose exposed HepG2 cells. Curcumin inhibited the elevated expression of these enzymes, transporters, and receptors in cancer cells. Curcumin also uplifted the SDH expression, which was inhibited in high glucose condition. Taken together, the findings of the present investigation first time demonstrate the ability of curcumin against high glucose-induced chemoresistance, along with its molecular mechanism. This will have implication in therapeutic management of malignancies in diabetic conditions.

Current understanding of the impact of COVID-19 on gastrointestinal disease: Challenges and openings.

The novel coronavirus disease-2019 (COVID-19) is caused by a positive-sense single-stranded RNA virus which belongs to the Coronaviridae family. In March 2019 the World Health Organization declared that COVID-19 was a pandemic. COVID-19 patients typically have a fever, dry cough, dyspnea, fatigue, and anosmia. Some patients also report gastrointestinal (GI) symptoms, including diarrhea, nausea, vomiting, and abdominal pain, as well as liver enzyme abnormalities. Surprisingly, many studies have found severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA in rectal swabs and stool specimens of asymptomatic COVID-19 patients. In addition, viral receptor angiotensin-converting enzyme 2 and transmembrane protease serine-type 2, were also found to be highly expressed in gastrointestinal epithelial cells of the intestinal mucosa. Furthermore, SARS-CoV-2 can dynamically infect and replicate in both GI and liver cells. Taken together these results indicate that the GI tract is a potential target of SARS-CoV-2. Therefore, the present review summarizes the vital information available to date on COVID-19 and its impact on GI aspects.

Molecular mechanism, diagnosis, and potential treatment for novel coronavirus (COVID-19): a current literature review and perspective.

Novel coronavirus disease 2019 (COVID-19) is a positive-sense single-stranded RNA virus which belongs to the Coronaviridae family. COVID-19 outbreak became evident after the severe acute respiratory syndrome coronavirus and the Middle East respiratory syndrome coronavirus in the twenty-first century as the start of the third deadly coronavirus. Currently, research is at an early stage, and the exact etiological dimensions of COVID-19 are unknown. Several candidate drugs and plasma therapy have been considered and evaluated for the treatment of severe COVID-19 patients. These include clinically available drugs such as chloroquine, hydroxychloroquine, and lopinavir/ritonavir. However, understanding the pathogenic mechanisms of this virus is critical for predicting interaction with humans. Based on recent evidence, we have summarized the current virus biology in terms of the possible understanding of the various pathophysiologies, molecular mechanisms, recent efficient diagnostics, and therapeutic approaches to control the disease. In addition, we briefly reviewed the biochemistry of leading candidates for novel therapies and their current status in clinical trials. As information from COVID-19 is evolving rapidly, this review will help the researcher to consider new insights and potential therapeutic approaches based on up-to-date knowledge. Finally, this review illustrates a list of alternative therapeutic solutions for a viral infection.

Erythrocyte microRNAs: a tiny magic bullet with great potential for sickle cell disease therapy.

Sickle cell disease (SCD) is a severe hereditary blood disorder caused by a mutation of the beta-globin gene, which results in a substantial reduction in life expectancy. Many studies are focused on various novel therapeutic strategies that include re-activation of the γ-globin gene. Among them, expression therapy caused by the fetal hemoglobin (HbF) at a later age is highly successful. The induction of HbF is one of the dominant genetic modulators of the hematological and clinical characteristics of SCD. In fact, HbF compensates for the abnormal beta chain and has an ameliorant effect on clinical complications. Erythropoiesis is a multi-step process that involves the proliferation and differentiation of a small population of hematopoietic stem cells and is affected by several factors, including signaling pathways, transcription factors, and small non-coding RNAs (miRNAs). miRNAs play a regulatory role through complex networks that control several epigenetic mechanisms as well as the post-transcriptional regulation of multiple genes. In this review, we briefly describe the current understanding of interactions between miRNAs, their molecular targets, and their regulatory effects in HbF induction in SCD.

Dynamic Propagation and Impact of Pandemic Influenza A (2009 H1N1) in Children: A Detailed Review.

Influenza is a highly contagious respiratory infection caused by the circulating Swine flu virus. According to the World Health Organization (WHO), the unique blending strain of influenza A H1N1 2009 (Swine Flu) is a pandemic affecting several geographical regions, including India. Previous literature indicates that children are "drivers" of influenza pandemics. At present, satisfactory data were not available to accurately estimate the role of children in the spread of influenza (in particular 2009 pandemic influenza). However, the role of children in the spread of pandemics influenza is unclear. Several studies in children have indicated that the immunization program decreased the occurrence of influenza, emphasizing the significance of communities impacted by global immunization programs. This article provides a brief overview on how children are a key contributor to pandemic Influenza A (2009 H1N1) and we would like to draw your attention to the need for a new vaccine for children to improve disease prevention and a positive impact on the community.

Curcumin, a traditional spice component, can hold the promise against COVID-19?

The severity of the recent pandemic and the absence of any specific medication impelled the identification of existing drugs with potential in the treatment of Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Curcumin, known for its pharmacological abilities especially as an anti-inflammatory agent, can be hypothesized as a potential candidate in the therapeutic regimen. COVID-19 has an assorted range of pathophysiological consequences, including pulmonary damage, elevated inflammatory response, coagulopathy, and multi-organ damage. This review summarizes the several evidences for the pharmacological benefits of curcumin in COVID-19-associated clinical manifestations. Curcumin can be appraised to hinder cellular entry, replication of SARS-CoV-2, and to prevent and repair COVID-19-associated damage of pneumocytes, renal cells, cardiomyocytes, hematopoietic stem cells, etc. The modulation and protective effect of curcumin on cytokine storm-related disorders are also discussed. Collectively, this review provides grounds for its clinical evaluation in the therapeutic management of SARS-CoV-2 infection.