Aim: To investigate pharmacodynamic interaction of Cyamopsis tetragonoloba (Cluster beans or guar beans) with acarbose on type-2 antidiabetic targets alpha-glucosidase and alpha-amylase. Background: The simultaneous use of herbal and ayurvedic medicines along with allopathic medicines is a common practice in India, without knowing their interactions. In particular, diabetic patients often use a combination of herbal, ayurvedic, and allopathic medications to achieve better results. Cyamopsis tetragonoloba (also known as cluster beans or guar beans), a popular vegetable in India, is thought to provide potential advantages for diabetes patients. Therefore, it was thought worthwhile to investigate pharmacodynamic interaction of Cyamopsis tetragonoloba (Cluster beans or guar beans) with a type-2 antidiabetic drug acarbose. Materials and Methods: In the current study, an aqueous and ethanol extract of Cyamopsis tetragonoloba was prepared and tested for antidiabetic activity in vitro and in vivo in combination with acarbose. At first, the Cyamopsis tetragonoloba extracts have been tested for their ability to adsorb glucose and inhibit alpha-amylase and alpha-glucosidase.Then, an oral glucose tolerance test, acute and subacute study for Cyamopsis tetragonoloba extracts and acarbose was conducted on male albino Wister rats. Results: The present results demonstrate the co-administration of aqueous extract and ethanol extract with acarbose have shown statistically significant reduction in blood glucose level in streptozotocin induced male diabetic rats. The aqueous extract with acarbose was more effective for postprandial hyperglycemia compares to ethanol extract with acarbose and acarbose. The additive pharmacological effect on blood glucose level has been observed after the co administration of extract of C. tetragonoloba with acarbose in streptozotocin induced male diabetic rats. Conclusion:To summarise, the interaction of herbal and pharmaceutical medicines is a critical to both patients and health care practitioners. It is necessary to continue research on potential risks and benefits associated with the combination of C. tetragonoloba and Acarbose on pharmacokinetic aspects. Such data is crucial for the formulation of future clinical guidelines to improve health-care outcomes in diabetes.

Orthobunyaviruses are linked to a broad spectrum of neurological disorders. However, the molecular determinants governing bunyavirus neuropathogenesis remain poorly understood, precluding the identification of drugs able to alleviate virus-induced neuronal dysfunctions. Here, we show that the prevalent, yet neglected, orthobunyavirus Ťahyňa virus (TAHV) disrupts neuronal integrity and proteostasis in human cerebral organoids (hCO), significantly decreasing synaptic protein expression and density. Moreover, TAHV-induced synaptic remodeling is associated with perturbed local field potential in organotypic cultures of human post-mortem adult brain explants (OPAB) and higher expression of the metabotropic Glutamate receptor 1 (mGluR1) in mice in the absence of overt neurological disease or neuroinflammation. Using proteome-based network medicine, we identified gabapentin as a therapeutic candidate that restores neurotransmitter receptor levels back to baseline in mice, and prevents TAHV-induced hyperexcitability in OPAB. Together, our data highlights the underappreciated neuropathological potential of a neglected orthobunyavirus, that interferes with neural integrity and neurotransmission, while neuromodulatory interventions may help to preserve cerebral functions. his study reveals the neuropathologic potential of the neglected Tahyna virus, and presents a powerful pipeline to discover antivirals that target the consequences of an infection (disorder oriented) rather than the infection itself (viro-centric).

Antibiotic resistance in Helicobacter pylori is an important factor in the ineffectiveness of eradication regimens. The rate of resistance is not constant and varies widely by region and over time. Resistance is mainly due to point mutations in target genes like 23S rRNA (clarithromycin), gyrA/gyrB (fluoroquinolones), rdxA/frxA (metronidazole), and PBP1 (amoxicillin). Moreover, multi-drug resistance is mediated by efflux proteins (e.g., HefA, RND proteins), biofilm formation, and phase-variable epigenetics like DNA methylation, which regulate virulence and stress response. Immune evasion by the bacterium involves Toll-like receptor modulation, cytokine (IL-1β, TNF-α, IL-8) dysregulation, miRNA (e.g., miR-146, miR-155) modification, and persistent epigenetic field defects post-eradication, which may result in carcinogenesis via NF-κB and STAT3 signaling. H. pylori also induces gastric microbiome dysbiosis, with reduced microbial diversity, increased pro-inflammatory species, and extragastric manifestations like iron deficiency anemia, metabolic syndrome, and neurological complications. Microbiome-directed therapies, such as probiotics (Lactobacillus, Bifidobacterium), have been demonstrated to increase eradication success to 78-88%. Machine learning algorithms, including XGBoost and CNNs, accurately predict resistance from genomic sequences with over 90% sensitivity, integrating multi-omics for personalized therapy. Efflux pumps are key in multidrug resistance, while host epigenetics plays a role in bacterial persistence. Approaches include susceptibility testing, bismuth quadruple therapy, and novel adjuncts such as fecal microbiota transplantation. Prompt and personalized eradication is essential in overcoming antimicrobial resistance and preventing oncogenic transformation.

BACKGROUND:Gastric cancer (GC) is a leading cause of cancer-related mortality worldwide, with Helicobacter pylori (H. pylori) infection recognized as a significant risk factor. H. pylori infects approximately 50% of the global population, contributing to chronic gastritis, peptic ulcers, and the development of GC. The oncoprotein Gankyrin (PSMD10) has been implicated in various human cancers, including hepatocellular carcinoma, gastric cancer, and lung cancer, by modulating autophagy and inflammatory pathways. METHODS:In this study, we explored the role of Gankyrin in H. pylori-induced gastric tumorigenesis via a Swiss albino mouse xenograft model. Mice were subcutaneously injected with H. pylori-infected AGS cells with or without Gankyrin knockdown. RESULTS:We assessed tumor growth and inflammatory markers (TNF-α and IL-6) levels and Gankyrin's downstream signaling molecules (p53, pRb, and NF-κB). Our results demonstrated that Gankyrin knockdown significantly decreased tumor formation in Swiss albino mice engrafted with H. Pylori-infected AGS cells. Notably, treatment with cyclosporine A significantly decreased the expression of TNF-α in all the AGS-engrafted mice except the PBS group. Moreover, our results show that the downregulation of Gankyrin significantly elevated the expression of NF-κB, pRb, and p53. CONCLUSION:These findings suggest that Gankyrin plays a crucial role in H. pylori-mediated GC progression by modulating inflammatory and tumor suppressor pathways. Targeting Gankyrin could provide a therapeutic strategy to mitigate the development of GC associated with H. pylori infection.

In the present study, we investigated biochemical, hematological, lipidomic, and metabolomic alterations associated with different SAR-CoV-2 variants of concern (VOCs), such as WT, α, β, γ, and δ, as well as their impact on COVID-19 severity. Across the first and second waves in India, a machine learning approach was used in 3134 COVID-19 patients, and nine critical biochemical and hematological parameters, namely, C-reactive protein (CRP), D-dimer, ferritin, neutrophil, WBC count, lymphocyte, urea, creatine, and lactate dehydrogenase (LDH), were identified. Furthermore, through metabolic and lipidomic profiles of lung and colon cells transfected with spike VOCs, notable dysregulation was exhibited by the delta variant correlated with characteristic pathways such as catecholamine and thyroid hormone synthesis. A corroborating meta-analysis also highlighted the involvement of urea and amino acid metabolism pathways. Overall, our study provides crucial insights into metabolic and biochemical disruptions caused by VOCs, contributing to a better understanding of COVID-19 pathogenesis and the development of targeted interventions.

Biological barriers, including blood-brain barrier (BBB) and gut epithelial barrier, are essential to maintain homeostasis and provide protection against pathogenic stress. Here, we investigated the impact of Helicobacter pylori -Epstein Barr Virus coinfection on gut-brain axis integrity. Our results demonstrate that coinfection induces significant disruptions in tight and adherens junction (TJ and AJ respectively) proteins in gastric epithelial cells, including downregulation of ZO-1 and E-cadherin. The secretome from these coinfected cells significantly compromises the integrity of BBB-derived endothelial cells, including cleavage of VE-cadherin, loss of TJ proteins such as Claudin-5, and enhanced permeability. Furthermore, the sole exposure of mice to coinfected secretome lead to the loss of cerebral VE-cadherin and ZO-1 and the induction of neuroinflammation, characterized by elevated pro-inflammatory cytokines, TNF-α, amyloidogenic accumulation, and neurocognitive deficits. The secretome driving such forces potentially carries pathogenic metabolites, host inflammatory cytokines and metabolites that might contribute to disease pathogenesis as observed in this study. Together, our current study provides novel insights into how coinfections contribute to gut-brain axis dysregulation and neurological pathogenesis. ![Figure][1] Graphical Abstract [1]: pending:yes

Rabies, caused by the neurotropic rabies virus, remains a significant public health concern worldwide. It remains a deadly zoonotic disease with a near 100% fatality rate once clinical symptoms manifest, causing about 59,000 deaths annually, of which 59.6% occur in Asia and 36.4% in Africa. Dog-mediated rabies accounts for over 99% of human cases. This review provides a comprehensive overview of rabies, covering its epidemiology, pathogenesis, Etiology, and developments in rabies vaccines. Once the virus enters the body through the bite of an infected animal it travels via peripheral nerves to the central nervous system, leading to fatal encephalitis if left untreated. Vaccination of domestic animals plays a pivotal role in preventing transmission to humans. Post-exposure prophylaxis (PEP) remains the cornerstone of rabies prevention in individuals exposed to potentially infected animals, comprising rabies vaccine and Rabies immunoglobulin administration. Advances in molecular virology have shed light on the pathogenesis of rabies, revealing the intricate interactions between the virus and the host immune system. Despite decades of research, treatment options for established rabies infection remain limited, emphasizing the importance of preventive measures. Experimental therapies, including monoclonal antibodies and novel antiviral agents, promise to improve outcomes in rabies patients. Regardless of the established efficacy of rabies vaccines, challenges remain in ensuring widespread accessibility and coverage, particularly in resource-limited regions. Strategies to enhance pre-exposure prophylaxis with affordable vaccine delivery are essential for achieving global rabies control and elimination goals, underscoring the need for sustained surveillance, vaccination, and public awareness efforts. Continued research into the virology and immunology of rabies is essential for the development of novel interventions to combat this deadly disease.

The Epstein-Barr virus (EBV) proteins EBNA1, LMP1, BZLF1, and gp350 have been consistently detected in the cerebrospinal fluid of patients with neurological disorders. Among these viral proteins, gp350 plays a critical role in determining viral tropism. In this study, phytocompounds were screened against the extra-virion domain of gp350. Based on their binding affinities, the top hits were subsequently subjected to 100-ns molecular dynamics simulations. Two phytocompounds, demethoxycurcumin (DMC) and rosmarinic acid (RA) were prioritized for subsequent in-vitro and in-vivo validation. Both compounds exhibited potent anti-gp350 activity in neuronal cells. Additionally, DMC- and RA-treated samples showed reduced levels of neuroinflammatory markers, including IL-6, TNF-α, NF-kB, and STAT3, compared with positive controls (acyclovir- or fingolimod-treated samples). Behavioral assays in mice revealed improved spatial memory in DMC- and RA-treated groups. Histological analyses demonstrated that EBV-infected mice displayed a disorganized hippocampal architecture relative to wild-type littermates, whereas hippocampal morphology was preserved in DMC- and RA-treated mice. Collectively, these findings indicate that DMC and RA exert significant anti-gp350 and neuroprotective effects and may hold potential as prophylactic and therapeutic candidates against EBV-associated neurodegeneration.

High mortality has been reported in severe cases of COVID-19. Emerging reports suggested that the severity is not only due to SARS-CoV-2 infection, but also due to coinfections by other pathogens exhibiting symptoms like COVID-19. During the COVID-19 pandemic, simultaneous respiratory coinfections with various viral (Retroviridae, Flaviviridae, Orthomyxoviridae, and Picoviridae) and bacterial (Mycobacteriaceae, Mycoplasmataceae, Enterobacteriaceae and Helicobacteraceae) families have been observed. These pathogens intensify disease severity by potentially augmenting SARSCoV-2 replication, inflammation, and modulation of signaling pathways. Coinfection emerges as a critical determinant of COVID-19 severity, principally instigated by heightened pro-inflammatory cytokine levels, as cytokine storm. Thereby, in co-infection scenario, the severity is also driven by the modulation of inflammatory signaling pathways by both pathogens possibly associated with interleukin, interferon, and cell death exacerbating the severity. In the current review, we attempt to understand the role of co- infections by other pathogens and their involvement in the severity of COVID-19.

The reactivation of ubiquitously present Epstein–Barr virus (EBV) is known to be involved with numerous diseases, including neurological ailments. A recent in vitro study from our group unveiled the association of EBV and its 12-amino acid peptide glycoprotein M146–157 (gM146–157) with neurodegenerative diseases, viz., Alzheimer's disease (AD) and multiple sclerosis. In this study, we have further validated this association at the in vivo level. The exposure of EBV/gM146–157 to mice causes a decline in the cognitive ability with a concomitant increase in anxiety-like symptoms through behavioral assays. Disorganization of hippocampal neurons, cell shrinkage, pyknosis, and apoptotic appendages were observed in the brains of infected mice. Inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were found to be elevated in infected mouse brain tissue samples, whereas TNF-α exhibited a decline in the serum of these mice. Further, the altered levels of nuclear factor-kappa B (NF-kB) and neurotensin receptor 2 affirmed neuroinflammation in infected mouse brain samples. Similarly, the risk factor of AD, apolipoprotein E4 (ApoE4), was also found to be elevated at the protein level in EBV/gM146–157 challenged mice. Furthermore, we also observed an increased level of myelin basic protein in the brain cortex. Altogether, our results suggested an integral connection of EBV and its gM146–157 peptide to the neuropathologies.

Coinfection of pathogenic bacteria and viruses is associated with multiple diseases. During the COVID-19 pandemic, the co-infection of other pathogens with SARS-CoV-2 was one of the important determinants of the severity. Although primarily a respiratory virus gastric manifestation of the SARS-CoV-2 infection was widely reported. This study highlights the possible consequences of SARS-CoV-2 -Helicobacter pylori coinfection in the gastrointestinal cells. We utilized the transfection and infection model for SARS-CoV-2 spike Delta (δ) and H. pylori respectively in colon carcinoma cell line HT-29 to develop the coinfection model to study inflammation, mitochondrial function, and cell death. The results demonstrate increased transcript levels of inflammatory markers like TLR2 (p < 0.01), IL10 (p < 0.05), TNFα (p < 0.05) and CXCL1 (p < 0.05) in pre-H. pylori infected cells as compared to the control. The protein levels of the β-Catenin (p < 0.01) and c-Myc (p < 0.01) were also significantly elevated in pre-H. pylori infected group in case of co-infection. Further investigation of apoptotic and necrotic markers (Caspase-3, Caspase-8, and RIP-1) reveals a necroptotic cell death in the coinfected cells. The infection and coinfection also damage the mitochondria in HT-29 cells, further implicating mitochondrial dysfunction in the necrotic cell death process. Our study also highlights the detrimental effect of pre-H. pylori exposure in the coinfection model compared to post-exposure and lone infection of H. pylori and SARS-CoV-2. This knowledge could aid in developing targeted interventions and therapeutic strategies to mitigate the severity of COVID-19 and improve patient outcomes.

Background: Breast cancer is the most commonly diagnosed cancer worldwide with 2.26 million cases in 2020. Cancer heterogeneity is the major challenge before existing therapeutic modalities due to metabolic variability of the cells as Warburg and anti-Warburg both type of metabolic phenotypes has been reported as a major contributing factors for cancer progression, invasion, metastasis and relapse. Also, this metabolic variability is associated with chemo and radio-resistance and poor therapeutic outcomes. Therefore, in present study we put an attempt to understand how simvastatin exert its effects on two metabolically different cell types and second how this drug can affect mitochondrial biomass, mt-DNA and glycolysis in both the cell types.Methods: We have observed effects of simvastatin on MCF-7 (dependent more on OXPHOS) and MDA-MB-231 (TNBC; more glycolytic with defected mitochondria) cells alone and after simvastatin pre-treatment followed by cytotoxic drugs including cisplatin, doxorubicin, gemcitabine, vincristine. We have conducted MTT assay for viability, cell death detection assay, apoptotic morphology study, scratch assay, transwell migration assay, lactate estimation in media (glycolysis parameter), mtDNA to n-DNA ratio, mitotracker red (for mitochondrial membrane potential) and mitotracker green staining (for mitochondrial biomass) and qPCR to study expression of mitochondrial transcription factors and apoptotic genes including PGC-1 alpha, NRF-1, NRF-2, TFAM, Bcl-2 and Bax.Results: We observed that 20 mu M simvastatin (SIM) was most efficient dose for MCF-7, whereas 12.5 mu M for MDA-MB-231 cells. Simvastatin itself caused a significant decrease in viability, increased cell death, and diminished wound closure in scratch assay as well as inhibited transwell migration. Also, the cells pre-treated with simvastatin for 72 h followed by treatment with cytotoxic drugs for 48 h increased chemo-sensitivity of cisplatin (CIS), doxorubicin (DOX), gemcitabine (GEM) and vincristine (VIN). SIM alone and in pre-treatment followed by cytotoxic drug treatment studies, there was a significant decrease in mitochondrial biomass and mitochondrial membrane potential (MMP), but also decreased glycolysis as evidenced by decrease in lactate levels in culture media. For inhibition of migratory potential, it was in the following order: CIS > VIN >DOX> GEM, which was in the same order to diminish mitochondrial functionality (mt-DNA/n-DNA ratio, mitotracker green staining and a significant decrease in the expression of transcriptional factors of mitochondrial biogenesis). Contrastingly a decrease in the same order was observed in lactate concentration independent to the mitochondrial loss, but probably via inherent ability of the drugs to reduce lactate and glycolysis. However, for cell death, apoptotic phenotype, diminished expression of Bcl-2 along with increase in Bax and loss of viability, the efficiency of simvastatin alone and in pre-treatment studies was in the following order: VIN > DOX>GEM>CIS, which was supported by loss of fluorescence of mitotracker red, suggested decrease in MMP; marker of cell death.Conclusion: We conclude that by using different doses simvastatin can target different metabolic phenotypes of breast cancer cells and can also increase the chemosensitivity of cytotoxic drugs, so that they can work efficiently at lower doses which will ultimately diminish the cost and toxicity issues.

Diabetes is prevailing in pandemic proportions, as nearly half a billion population is affected by diabetes worldwide. The expenditure on diabetes healthcare is estimated to grow to $845 billion by 2045. However, identifying an efficient drug for completely curing diabetes and its complications is still unattainable. Given these challenges, we have discussed the range of storage molecules and pigments derived from microalgae, macroalgae, and cyanobacteria and explored their promising potential as antidiabetic drugs. Further, in silico studies have also been investigated for elucidating plausible molecular mechanisms of the most promising algal compounds. It is noteworthy that the chemical synthesis of bulky compounds is a cumbersome and less efficient process, whereas naturally occurring bulky compounds have complex stereospecific ornamentation of chemical groups executed by the number of stereospecific enzymes. On the other hand, growing algae in controlled conditions is an easy method to get various algal metabolites with a diverse array of chemical structures exhibiting pleiotropic antidiabetic activities. This review highlights the promising potential of algal metabolites to treat diabetes by targeting a variety of molecular mechanisms involved in the pathogenesis of diabetes.

Context Soybeans (Glycine max. (L.) Merr.) are a major source of phospholipids, which are vital to human and animal nutrition, as well having many pharmaceutical and industrial applications. Identification of quantitative trait loci (QTLs) is a prerequisite for the development of high-phospholipid soybean genotypes through marker-assisted breeding. Aims We aimed to identify QTLs associated with biosynthesis of four phospholipids in soybean. Methods We developed two F2 populations comprising 233 and 254 plants, respectively, from two crosses (JS20-34 × AVKS215 and JS20-98 × AVKS215), and used 208 polymorphic simple sequence repeat markers found common to both F2 populations for linkage map construction. QTLs associated with four phospholipids, phosphatidylethanolamine (PE), phosphatidic acid (PA), phosphatidylinositol (PI) and phosphatidylcholine (PC), were analysed via inclusive composite interval mapping of additive QTLs using QTL IciMapping software. Key results In the respective F2 populations, we identified seven and six QTLs for PE, seven and nine QTLs for PA, and nine and eight QTLs for PC. Six QTLs were associated with PI in each population. Five QTLs for each of PA and PC, three QTLs for PE, and four QTLs for PI were found common to both F2 populations. Conclusions The results showed that some genomic regions such as Sat_341–Satt331 on chromosome 10, and Satt325–Sat_387 and Sat_229–Satt510 on chromosome 13, were associated with all four phospholipids in both F2 populations. QTLs associated with phospholipids were also found to be annotated with genes involved in phospholipid biosynthesis. Implications The QTLs identified may be useful in marker-assisted breeding for the development of soybean genotypes with high levels of phospholipids of interest and for identifying functional genes involved in phospholipid biosynthesis.

SARS-CoV-2 Envelope protein (E) is one of the crucial components in virus assembly and pathogenesis. The current study investigated its role in the SARS-CoV-2-mediated cell death and inflammation in lung and gastrointestinal epithelium and its effect on the gastrointestinal-lung axis. We observed that transfection of E protein increases the lysosomal pH and induces inflammation in the cell. The study utilizing Ethidium bromide/Acridine orange and Hoechst/Propidium iodide staining demonstrated necrotic cell death in E protein transfected cells. Our study revealed the role of the necroptotic marker RIPK1 in cell death. Additionally, inhibition of RIPK1 by its specific inhibitor Nec-1s exhibits recovery from cell death and inflammation manifested by reduced phosphorylation of NFκB. The E-transfected cells' conditioned media induced inflammation with differential expression of inflammatory markers compared to direct transfection in the gastrointestinal-lung axis. In conclusion, SARS-CoV-2 E mediates inflammation and necroptosis through RIPK1, and the E-expressing cells' secretion can modulate the gastrointestinal-lung axis. Based on the data of the present study, we believe that during severe COVID-19, necroptosis is an alternate mechanism of cell death besides ferroptosis, especially when the disease is not associated with drastic increase in serum ferritin.

During COVID-19 pandemic qRT-PCR, CT scans and biochemical parameters were studied to understand the patients' physiological changes and disease progression. There is a lack of clear understanding of the correlation of lung inflammation with biochemical parameters available. Among the 1136 patients studied, C-reactive-protein (CRP) is the most critical parameter for classifying symptomatic and asymptomatic groups. Elevated CRP is corroborated with increased D-dimer, Gamma-glutamyl-transferase (GGT), and urea levels in COVID-19 patients. To overcome the limitations of manual chest CT scoring system, we segmented the lungs and detected ground-glass-opacity (GGO) in specific lobes from 2D CT images by 2D U-Net-based deep learning (DL) approach. Our method shows $\ >\!90\%$ accuracy, compared to the manual method ( $\sim\!80\%$ ), which is subjected to the radiologist's experience. We determined a positive correlation of GGO in the right upper-middle (0.34) and lower (0.26) lobe with D-dimer. However, a modest correlation was observed with CRP, ferritin and other studied parameters. The final Dice Coefficient (or the F1 score) and Intersection-Over-Union for testing accuracy are 95.44% and 91.95%, respectively. This study can help reduce the burden and manual bias besides increasing the accuracy of GGO scoring. Further study on geographically diverse large populations may help to understand the association of the biochemical parameters and pattern of GGO in lung lobes with different SARS-CoV-2 Variants of Concern's disease pathogenesis in these populations.

H. pylori infection can lead to gastric diseases by modulating the various cellular processes such as cellular stress, apoptosis, autophagy, and metabolic changes. H. pylori exposed gastric epithelial cells bypass the cell death pathways. However, the underlying molecular mechanisms remain in infancy. Herein, we determined that H. pylori infection on gastric epithelial cells bypass the cell death pathway via the modulation of autophagy-related signaling molecules (LC3B and ATG7) through the host-associated oncoprotein Gankyrin. Upregulated expression of Gankyrin further enhanced the various antioxidant (gclm, gclc, sod2, cat, keap1, ant, and hsf1) and autophagy-associated genes’ transcripts (atg5, atg7, lc3b, beclin, and sqstm1). Elevated expression of Gankyrin also modulates the various downstream signaling proteins such as Akt, Beta-catenin, and NFkB. We also observed altered cancerous properties of gastric epithelial cells viz; apoptosis, wound healing, chemoresistance, biomass and membrane potential of mitochondria. Concisely, the study revealed that H. pylori infection promotes GC via autophagy through the modulation of oncoprotein Gankyrin and cellular reactive oxygen species (ROS). Overall, our study demonstrated the antiapoptotic property of H pylori-infected gastric epithelial cells might govern through Gankyrin-directed autophagy.

Background: As per facts sheet of WHO, cancer is a leading cause of mortality worldwide accounting nearly 10 million deaths in 2020. However, breast, lung, colon and rectum, prostate, skin and stomach cancers are the six most prevailing cancer across the globe. Out of the aforesaid cancers, breast cancer is the most commonly diagnosed cancer worldwide with 2.26 million cases in 2020.Summary: Metabolic alterations have been found to be associated with most of the cancers, suggesting that both loss of mitochondrial functioning (Warburg metabolism) as well as gain of mitochondrial functioning (OXPHOS) are contributing factor for cancer progression, invasion and metastasis. Here it is noteworthy that cancer is a heterogeneous mass of the cells and different cell types are having different tactics due to difference in tumor microenvironment, clonal selection, clonal evolution and cancer stem cell formation which resultantly affects the overall therapeutic response of the cancer therapies, chemo-resistance, radio-resistance, cancer stem cell formation, angiogenesis, migratory potential, invasion-metastasis cascade etc. Cancer cells are having a great metabolic plasticity which supports their survival, proliferation, invasion, metastasis and relapse. Variety of metabolic drugs are already in clinical practice for various metabolic disorders and are known for their proven safety and efficacy track record since decades and they have been reported for pleitropic influence on mitochondrial metabolism as well as biogenesis. Similarly, some other emerging pro- and anti-oxidative drugs for mitochondrial reactive oxygen species are also known to modulate mitochondrial functioning by various means. Therefore, present review sheds light on the potential of metabolic drugs and mitochondrial modulators on cancer pathologies and their underlying molecular mechanisms through which they may improve clinical outcomes and prognosis of cancer patients by many folds.