Negative impacts of COVID-19 on human health and economic and social activities urge scientists to develop effective treatments. Baicalin is a natural flavonoid, extracted from a traditional medicinal plant, previously reported with anti-inflammatory activity. In this study, we used pharmacophore fitting and molecular docking to screen and determine docking patterns and the binding affinity of baicalin on 3 major targets of SARS-CoV-2 (3-chymotrypsin-like cysteine protease [3CLpro], papain-like protease [PLpro], and RNA-dependent RNA polymerase). The obtained data revealed that baicalin has high pharmacophore fitting on 3CLpro and predicted good binding affinity on PLpro. Moreover, using the enzymatic assay, we examined the inhibitory effect of baicalin in vitro on the screened enzymes. Baicalin also exhibits inhibitory effect on these proteases in vitro. Additionally, we performed pharmacophore-based screening of baicalin on human targets and conducted pathway analysis to explore the potential cytoprotective effects of baicalin in the host cell that may be beneficial for COVID-19 treatment. The result suggested that baicalin has multiple targets in human cell that may induce multiple pharmacological effects. The result of pathway analysis implied that these targets may be associated with baicalin-induced bioactivities that are involved with signals of pro-inflammation factors, such as cytokine and chemokine. Taken together with supportive data from the literature, the bioactivities of bailalin may be beneficial for COVID-19 treatment by reducing cytokine-induced acute inflammation. In conclusion, baicalin is potentially a good candidate for developing new therapeutic to treat COVID-19.

Novel quinazolinone compounds have been studied in the field of drug discovery for a long time. Among their broad range of pharmacological effects, certain compounds effectively inhibit cancer cell proliferation. MJ‑33 is a quinazolinone derivative with proposed anticancer activities that was synthesized in our laboratory. The present study aimed to evaluate the anticancer activity of MJ‑33 in fluorouracil (5FU)‑resistant colorectal cancer cells (HT‑29/5FUR) and to investigate the underlying molecular mechanisms. The cell viability assay results indicated that HT‑29/5FUR cell viability was inhibited by MJ‑33 treatment in a concentration‑dependent manner compared with the control group. The cellular morphological alterations observed following MJ‑33 treatment indicated the occurrence of apoptosis and autophagy, as well as inhibition of cell proliferation in a time‑dependent manner compared with the control group. The acridine orange, LysoTracker Red and LC3‑green fluorescent protein staining results indicated that MJ‑33 treatment significantly induced autophagy compared with the control group. The DAPI/TUNEL dual staining results demonstrated increased nuclear fragmentation and condensation following MJ‑33 treatment compared with the control group. The Annexin V apoptosis assay and image cytometry analysis results demonstrated a significant increase in apoptotic cells following MJ‑33 treatment compared with the control group. The western blotting results demonstrated markedly decreased Bcl‑2, phosphorylated (p)‑BAD, pro‑caspase‑9 and pro‑caspase‑3 expression levels, and notably increased cytochrome c and apoptotic peptidase activating factor 1 expression levels following MJ‑33 treatment compared with the control group. Moreover, the expression levels of autophagy‑related proteins, including autophagy related (ATG)‑5, ATG‑7, ATG‑12, ATG‑16, p62 and LC3‑II, were increased following MJ‑33 treatment compared with the control group. Furthermore, MJ‑33‑treated HT‑29/5FUR cells displayed decreased expression levels of p‑AKT and p‑mTOR compared with control cells. The results suggested that MJ‑33‑induced apoptosis was mediated by AKT signaling, and subsequently modulated via the mitochondria‑dependent signaling pathway. Therefore, the results suggested that suppression of AKT/mTOR activity triggered autophagy in the HT‑29/5FUR cell line. In summary, the results indicated that MJ‑33 inhibited HT‑29/5FUR cell viability, and induced apoptosis and autophagy via the AKT/mTOR signaling pathway. The present study may provide novel insight into the anticancer effects and mechanisms underlying MJ‑33 in 5FU‑resistant colorectal cancer cells.

Background and Aims: Fish oil and krill oil are primary sources of Omega-3 polyunsaturated fatty acids (PUFAs), differing in their molecular forms and bioavailability. Understanding these differences can optimize their therapeutic use. This study aims to compare the bioavailability of Omega-3 PUFAs in fish oil and krill oil using a network meta-analysis approach. By evaluating various molecular forms and dosages, the study seeks to identify the most effective Omega-3 sources and dosing regimens to maximize health benefits.

Coronavirus disease 2019 (COVID‐19) has been spreading worldwide with a mind-boggling speed. According to a statement from World Health Organization (WHO), COVID-19 has infected more than six billions people and caused more than one and half million passing in the world. Based on previous experience with SARS, the Taiwanese government had decided to block viral transmission during its early stages. This review sums up the clinical characteristics, Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) viral infection process, diagnostic methods, preventive strategy, and the executive proportions of COVID-19, as well as the name-based mask distribution system (NBMDS) in Taiwan. We also give a review of the conceivable sub-atomic pharmacologic systems against SARS-CoV-2 specialists and the blend of remdesivir (GS-5734), chloroquine (CQ), and hydroxychloroquine (HCQ). Lastly, we summarized the therapeutic agents against COVID-19 as mentioned by COVID-19 treatment guidelines. In this review, development of novel anti-SARS-CoV-2 viral agents, vaccines for COVID-19 therapy or an effective combination therapy can be expected based on all the information accumulated. Last but not least, we might want to stretch out our best respects to all medical providers in their worldwide battle against COVID-19.

Antioxidant therapy is gaining traction in managing sepsis and septic shock, owing to its perceived positive impact on patient outcomes. This study sought to compare the efficacy of five antioxidant therapies (melatonin, vitamin C, vitamin E, selenium, and N-acetylcysteine, both individually and in combination with other compounds such as vitamin B1, hydrocortisone, propolis, and glutamine) in treating sepsis or septic shock in the intensive care unit (ICU). The study involved randomized and multi-arm trials with sepsis or septic shock patients using melatonin, vitamin C, vitamin E, selenium, or N-acetylcysteine. Studies were sourced from PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and WHO - Clinical Trials Registry Platform for the frequentist network meta-analysis on 28-day mortality and Sequential Organ Failure Assessment (SOFA) scores. The risk of bias was assessed using the Physiotherapy Evidence Database scale. Therapies were compared directly and indirectly using R software. The study of 56 trials involving 9,366 patients was included. Bias assessment revealed that 89.3 % of trials achieved excellent or good quality. Based on treatment ranking and pairwise comparisons, melatonin with propolis (SUCRA = 93.29 %) is effective in improving SOFA scores, statistically significant, with no publication bias (p= 0.73). High-dose vitamin C (SUCRA = 83.97 %), vitamin C with vitamin B1 (SUCRA = 78.72 %), and melatonin (SUCRA = 67.03 %) are potential therapies for organ dysfunction. Melatonin (SUCRA = 88.22 %) and high-dose vitamin C (SUCRA = 80.75 %) were the most effective in reducing 28-day mortality rates. However, analysis indicated that the results for 28-day mortality rates were not statistically significant. Also, these results contained publication bias (p= 0.02). The study offers fresh perspectives on antioxidant therapy treatments for sepsis or septic shock in ICU, emphasizing the combination of melatonin and propolis notably reduces SOFA scores for those patients.