The World Health Organization, has declared the recent multiregional outbreak of monkeypox, a global public health emergency. Monkeypox is a zoonotic viral infection endemic to the west and central Africa. It belongs to the Poxviridae family, the Chordopoxvirinae subfamily, and the Orthopoxvirus genus. The Poxviridae family generally consists of complex, large, enveloped, and linear double-stranded DNA viruses. The initial clinical symptoms of monkeypox are often fever, severe headache, lymphadenopathy, myalgia, and fatigue. The skin lesions typically erupt within 1–3 days of the onset of fever. The rash tends to be more localized on the face and extremities than on the trunk. Monkeypox is often a self-limiting infection, and symptoms last from 2 to 4 weeks. It is isolated from various species, but the exact natural host is uncertain. Monkeypox is transmitted by close contact with infected humans or animals. Currently, no specific medication is available for monkeypox, and the existing therapeutics are the anti-viral agents approved for smallpox infection, including tecovirimat, cidofovir, and brincidofovir. Additionally, the U.S. Food and Drug Administration has approved Vaccinia Immune Globulin Intravenous for treating vaccination complications. It is diagnosed by PCR. There are currently two vaccines licensed by the U.S. Food and Drug Administration. According to the WHO guidance, the first-generation smallpox vaccines held in national reserves of some countries are not recommended as they do not meet the current safety and manufacturing standards. The interim guidance indicates that new and safer (second- and third generation) vaccines for smallpox, may be beneficial for monkeypox prevention, including JYNNEOS, which has been approved for the prevention of monkeypox. Human monkeypox was first reported in 1970. Since then, it has caused several outbreaks, mainly in central and west Africa. The first monkeypox outbreak outside of Africa occurred in the United States in 2003, linked to contact with infected pet prairie dogs. More recently (2018-2021), monkeypox cases have been reported in travelers from Nigeria to the United Kingdom, Israel, Singapore, and the US. Since May 2022, multiple monkeypox cases have been confirmed in several non-endemic countries, raising the concern of an emerging global pandemic. This review is an updated overview of our current state of knowledge regarding monkeypox virology, pathophysiology, clinical characteristics, epidemiology, vaccines, diagnosis, and treatment options.

High mortality in pancreatic cancer patients is partly due to resistance to chemotherapy. We describe that human pancreatic cancer cells acquire drug resistance by a novel mechanism in which they expel and remove chemotherapeutic drugs from the microenvironment via microvesicles (MVs). Using human pancreatic cancer cells that exhibit varied sensitivity to gemcitabine (GEM), we show that GEM exposure triggers the cancer cells to release MVs in an amount that correlates with that cell line's sensitivity to GEM. The importance of MV-release in gaining drug resistance in GEM-resistant pancreatic cancer cells was confirmed when the inhibition of MV-release sensitized the cells to GEM treatment, both in vitro and in vivo. Mechanistically, MVs remove drugs that are internalized into the cells and that are in the microenvironment. The differences between the drug-resistant and drug-sensitive pancreatic cancer cell lines tested here are explained based on the variable content of influx/efflux proteins present on MVs, which directly dictates the ability of MVs either to trap GEM or to allow GEM to flow back to the microenvironment.

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1. Influx and efflux proteins play a major role in the overall uptake and efficacy of chemotherapeutic agents and cellular chemo-resistance. 2. The present study investigated the time course and dose dependency of the induction of three efflux proteins, P-gp, MRP1 and MRP5, in response to gemcitabine exposure in Capan-2 pancreatic cancer cell line at transcriptional and translational levels. The influence of exposure on the influx protein (ENT1), the net cellular uptake of the gemcitabine, the overall ATPase activity and the cell death rate were also measured. 3. The time course of the expression exhibited an initial rise, toward a plateau level. The estimated Km and Vmax confirmed that MRP5 and to a lesser extent MRP1 are the prominent proteins for efflux of gemcitabine. Both mRNA and protein expression demonstrated the time and concentration dependency of the induction; and the elevated ATPase activity validated that the induced efflux proteins are functionally active. 4. The results of the study revealed that the efficacy window of gemcitabine as it relates to the function of the efflux proteins is concentration and temporal dependent and is well correlated to the first 60 min of exposure.

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Covid-19 infection is associated with systemic inflammation, as do other infections. COVID-19 in some patients is associated with hyperinflammatory responses, which might lead to a cytokine storm. This phenomenon plays a major role in COVID-19 severity and death, and usually associated with poor disease prognosis. Higher levels of inflammatory hallmarks including C-reactive protein, ferritin, D-dimers, and cytokines such as L-6, IL-10, and TNF-α has been observed in severe cases of the disease. Many anti-viral drugs have been tried to eradicate the virus, none were proven fully effective. Supportive care and management of the complications that are caused mainly by inflammation might be the key element for greater survival rates and shorter periods of mechanical ventilation and overall hospitalization. However, the efficacy of these treatments still needs well-planned clinical trials. In such trials, careful attention must be paid to the duration of the treatment, the onset of beneficial effects, and the severity of the disease, otherwise, the outcomes may still remain inconclusive. Herein, we present a review of the current drugs, which are being used in the management of the disease and their anti-inflammatory properties. We also investigated if these drugs directly interact with ACE 2, which is a crucial component of the virus entry to the cells.

Objectives This meta-analysis evaluated the Efficacy and Effectiveness of several COVID-19 vaccines, including AstraZeneca, Pfizer, Moderna, Bharat, and Johnson & Johnson, to better estimate their immunogenicity, benefits, or side effects. Methods Studies reporting the Efficacy and Effectiveness of COVID-19 vaccines from November 2020 to April 2022 were included. The pooled Effectiveness/Efficacy with a 95% confidence interval (95% CI) with Metaprop order was calculated. The results were presented in forest plots. Predefined subgroup analyses and sensitivity analyses were also performed. Results A total of twenty articles were included in this meta-analysis. After the first dose of the vaccine, the total effectiveness of all COVID-19 vaccines in our study was 71% (95% CI 0.65, 0.78). The total effectiveness of vaccines after the second dose was 91% (95% CI 0.88, 0.94)). The total efficacy of vaccines after the first and second doses was 81% (95% CI 0.70, 0.91) and 71% (95% CI 0.62, 0.79), respectively. The effectiveness of the Moderna vaccine after the first and second dose was the highest among other studied vaccines ((74% (95% CI, 0.65, 0.83) and 93% (95% CI, 0.89, 0.97), respectively). The highest first dose overall effectiveness of the studied vaccines was against the Gamma variant (74% (95% CI, 0.73, 0.75)), and the highest effectiveness after the second dose was observed against the Beta variant (96% (95% CI, 0.96, 0.96)). The Efficacy for AstraZeneca and Pfizer vaccines after the first dose was 78% (95% CI, 0.62, 0.95) and 84% (95% CI, 0.77, 0.92), respectively. The second dose Efficacy for AstraZeneca, Pfizer, and Bharat was 67% (95% CI, 0.54, 0.80), 93% (95% CI, 0.85, 1.00), and 71% (95% CI, 0.61, 0.82), respectively. The overall efficacy of first and second dose vaccination against the Alfa variant was 84% (95% CI, 0.84, 0.84) and 77% (95% CI, 0.57, 0.97), respectively, the highest among other variants. Conclusion mRNA-based vaccines against COVID-19 showed the highest total efficacy and effectiveness than other vaccines. In general, administering the second dose produced a more reliable response and higher effectiveness than a single dose.

The aim of this study was to synthesize a peptide prodrug of glucosamine (GlcN) with increased gut permeability through the gut peptide transporter 1 (PepT1). Glycine-Valine ester derivative of GlcN (GVG) was synthesised using solid phase synthesis followed by characterization and evaluation of its physicochemical and intestinal stability. In addition, GVG was evaluated for its ability to be biotransformed to GlcN in the liver homogenate. In vitro absorption of the new prodrug through everted rat gut was also assessed. GVG demonstrated significant and meaningful increased gut permeability as compared with GlcN. It showed favorable stability in the gut and a quick cleavage to GlcN after exposure to the liver homogenate. In conclusion, a novel prodrug of glucosamine with superior gut permeability compared to GlcN was developed and successfully tested in vitro.