Multidimensional mechanisms of metformin in cancer treatment.

Metformin has been in clinical use for more than half a century, yet its molecular mechanism of action is not entirely understood. Metformin has been shown to have antiproliferative and synergistic effects on various types of cancers. The anticancer effects of metformin are potentially applicable to both diabetic and nondiabetic patients. Areas of ongoing investigation focus on metformin's ability to activate adenosine monophosphate kinase (AMPK), in addition to its effect on Myc mRNA, monocarboxylate transporter 1 (MCT1), hypoxia-inducible factor 1 (HIF1), mammalian target of rapamycin (mTOR), and human epidermal growth factor receptor 2 (HER2). Additional anticancer effects are exhibited by acting on liver kinase B1 (LKB1), CREB-regulated transcription coactivator 2 (CRTC2), nitric oxide, and reactive oxygen species. Further investigation will be focused on elucidating metformin's metal-binding properties and how they may be harnessed for their anticancer effect. The acquired knowledge about metformin properties has expanded the number of targets for drug discovery such as microRNA, hexokinase, adenylate cyclase, transcription factors, various cyclins, and copper. In order to design anticancer drugs that mimic metformin's mechanism of action, binding assay studies must be conducted to fully understand and utilize the AMPK-dependent and independent mechanisms. Metformin's complex mechanisms that can potentially make this drug a multifaceted therapy targeting tumorigenesis in addition to information from ongoing clinical trials implicate that metformin can be a potential chemotherapeutic drug or adjuvant that could prove to be vital to future strategies against several types of cancer.

Disseminated Mycobacterial Infection as a Sequelae of Bladder Biopsy.

Disseminated Mycobacterium infections have been commonly documented in the immunocompromised and patients who undergo treatment for non-muscle invasive bladder cancer with the Bacillus Calmette-Guerin vaccine; however, it was unique to our patient's case that she had no record of receiving vaccination in her native country, was immunocompetent, and had exposure to bovine livestock before immigrating to the United States. A 57-year-old woman with no significant medical history presented with complaints of abdominal pains and yellowing of her skin. Laboratory workup was consistent with cholestatic hepatitis. One month prior to presentation, she underwent biopsy and culture of an unspecified bladder mass, which turned out to be positive for Mycobacterium bovis. All antituberculosis medications were discontinued, without improvement of her symptoms and hepatic function tests. Subsequent liver biopsy showed the presence of granulomas with acid-fast bacilli; hence, disseminated infection was highly suspected. Multiple sputum cultures and quantiferon tests were negative, and other diagnostic tests were unremarkable. Initiation of appropriate antibiotics resulted in marked symptomatic improvement and gradual normalization of hepatic function parameters. Disseminated mycobacterial infection may present differently in patients; however, it is important to note that the source of primary infection may vary. Prompt diagnosis and treatment of these pathogens may lead to improved outcomes.

Ruxolitinib and the Mitigation of Severe COVID-19: A Systematic Review and Meta-analysis.

BACKGROUND: The cause of end-organ damage and acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19) patients is postulated to be connected to the uncontrolled increase of pro-inflammatory cytokines. The upregulation of many cytokines is dependent on signaling through the Janus kinase 1 (JAK-1) and JAK-2 pathways. Ruxolitinib, a JAK-1 and JAK-2 inhibitor, is documented to have potent anti-inflammatory activity by targeting several cytokines and growth factors with proposed efficacy in the cytokine storm observed in severe COVID-19 patients; therefore, this study examines the efficacy and tolerability of ruxolitinib for adult COVID-19 patients. MATERIALS AND METHODS: This review was conducted using preferred reporting items for aystematic reviews and meta-analyses (PRISMA) methodology. Six reviewers analyzed 1,120 results. Seven studies were selected and validated. A quantitative meta-analysis was further performed to evaluate clinical improvement at day 28, mortality at day 28, and oxygen requirements comparing treatment and standard of care groups. RESULTS: 168 individuals were involved in the studies selected: 122 in cohort studies, 4 in case reports, and 41 in randomized controlled studies. The ruxolitinib group had a higher likelihood of clinical improvement by the 28th day of treatment when assessed with the standard of care (SOC) group (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 0.53 - 4.16; P = 0.45; I² = 0%). The SOC group was at a higher risk of experiencing serious adverse events (OR: 0.17; 95% CI: 0.03 - 1.13; P = 0.07). Notably the SOC group had a higher likelihood of death (OR: 0.51; 95% CI: 0.11-2.29; P = 0.07; I² = 0%). CONCLUSION: Prior studies on ruxolitinib have demonstrated it is able to decrease inflammatory markers. In recent studies on COVID-19, treatment with ruxolitinib decreased the time on mechanical ventilation, hospitalization time, and the need for vasopressor support. Additionally, ruxolitinib showed decreased mortality and demonstrated improvement in lung congestion as evidenced by computerized tomography imaging. These findings warrant further clinical investigation into Ruxolitinib as a potential treatment approach for severe COVID-19.

Omega 3 Fatty Acids and COVID-19: A Comprehensive Review.

The rapid international spread of severe acute respiratory syndrome coronavirus 2 responsible for coronavirus disease 2019 (COVID-19) has posed a global health emergency in 2020. It has affected over 52 million people and led to over 1.29 million deaths worldwide, as of November 13th, 2020. Patients diagnosed with COVID-19 present with symptoms ranging from none to severe and include fever, shortness of breath, dry cough, anosmia, and gastrointestinal abnormalities. Severe complications are largely due to overdrive of the host immune system leading to "cytokine storm". This results in disseminated intravascular coagulation, acute respiratory distress syndrome, multiple organ dysfunction syndrome, and death. Due to its highly infectious nature and concerning mortality rate, every effort has been focused on prevention and creating new medications or repurposing old treatment options to ameliorate the suffering of COVID-19 patients including the immune dysregulation. Omega-3 fatty acids are known to be incorporated throughout the body into the bi-phospholipid layer of the cell membrane leading to the production of less pro-inflammatory mediators compared to other fatty acids that are more prevalent in the Western diet. In this article, the benefits of omega-3 fatty acids, especially eicosapentaenoic acid and docosahexaenoic acid, including their anti-inflammatory, immunomodulating, and possible antiviral effects have been discussed.