Industry 4.0 Technologies for the Manufacturing and Distribution of COVID-19 Vaccines.

BACKGROUND: The evolutionary stages of manufacturing have led us to conceptualize the use of Industry 4.0 for COVID-19 (coronavirus disease 2019), powered by Industry 4.0 technologies. Using applications of integrated process optimizations reliant on digitized data, we propose novel intelligent networks along the vaccine value chain. Vaccine 4.0 may enable maintenance processes, streamline logistics, and enable optimal production of COVID-19 vaccines. VACCINE 4.0 FRAMEWORK: The challenge in applying Vaccine 4.0 includes the requirement of large-scale technologies for digitally transforming manufacturing, producing, rolling-out, and distributing vaccines. With our framework, Vaccine 4.0 analytics will target process performance, process development, process stability, compliance, quality assessment, and optimized maintenance. The benefits of digitization during and post the COVID-19 pandemic include first, the continual assurance of process control, and second, the efficacy of big-data analytics in streamlining set parameter limits. Digitization including big data-analytics may potentially improve the quality of large-scale vaccine production, profitability, and manufacturing processes. The path to Vaccine 4.0 will enhance vaccine quality, improve efficacy, and compliance with data-regulated requirements. DISCUSSION: Fiscal and logistical barriers are prevalent across resource-limited countries worldwide. The Vaccine 4.0 framework accounts for expected barriers of manufacturing and equitably distributing COVID-19 vaccines. With amalgamating big data analytics and biometrics, we enable the identification of vulnerable populations who are at higher risk of disease transmission. Artificial intelligence powered sensors and robotics support thermostable vaccine distribution in limited capacity regions, globally. Biosensors isolate COVID-19 vaccinations with low or limited efficacy. Finally, Vaccine 4.0 blockchain systems address low- and middle-income countries with limited distribution capacities. CONCLUSION: Vaccine 4.0 is a viable framework to optimize manufacturing of vaccines during and post the COVID-19 pandemic.

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.

Variances in BCG protection against COVID-19 mortality: A global assessment.

The BCG vaccine is known to impart nonspecific immunological benefits alongside conferring protection to tuberculosis in endemic regions. It is also known to protect against bladder cancer and other respiratory tract infections. During the coronavirus disease 2019 (COVID-19) pandemic, the BCG vaccine has gained attention due to its role in conferring protective immunity. We demonstrate the potential immunological protective mechanisms that play a role against COVID-19. We conduct a global assessment of the countries that have the highest and lowest mortality rates determined by an a priori methodology. Lastly, we discuss the potential limitations of incorporating BCG vaccines as potential strategies against COVID-19 and provide recommendations regarding their use in ongoing and future epidemics.

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.