METHODS: An organic ethyl acetate extract of Penicillium verruculosum sponge-derived endophytic fungi from Spongia officinalis yielded seven different secondary metabolites which are purified through HPLC. The isolated compounds are of averufin (1), aspergilol-A (2), sulochrin (3), monomethyl sulochrin (4), methyl emodin (5), citreorosein (6), and diorcinol (7). All the seven isolated compounds were characterized by high-resolution NMR spectral studies. All isolated compounds', such as anticancer, antimicrobial, anti-tuberculosis, and antiviral, were subjected to bioactivity screening.
RESULTS: Out of seven tested compounds, compound (1) exhibits strong anticancer activity toward myeloid leukemia. HL60 cell lines have an IC50 concentration of 1.00μm, which is nearly significant to that of the standard anticancer drug taxol. A virtual computational molecular docking approach of averufin with HL60 antigens revealed that averufin binds strongly with the protein target alpha, beta-tubulin (1JFF), with a -10.98 binding score. Consecutive OSIRIS and Lipinski ADME pharmacokinetic validation of averufin with HL60 antigens revealed that averufin has good pharmacokinetic properties such as drug score, solubility, and mutagenic nature. Furthermore, aspergilol-A (2) is the first report on the Penicillium verruculosum fungal strain.
DISCUSSION: We concluded that averufin (1) isolated from Penicillium verruculosum can be taken for further preliminary clinical trials like animal model in-vivo studies and pharmacodynamic studies. A future prospect of in-vivo anticancer screening of averufin can be validated through the present experimental findings.
METHODS: This retrospective cohort study included 962 patients admitted to two hospitals in Kuwait with a confirmed diagnosis of COVID-19. Cumulative all-cause mortality rate was the primary outcome.
RESULTS: A total of 302 patients (males, 196 [64.9%]; mean age, 57.2 ± 14.6 years; mean body mass index, 29.8 ± 6.5 kg/m2) received anticoagulation therapy. Patients receiving anticoagulation treatment tended to have pneumonia (n = 275 [91.1%]) or acute respiratory distress syndrome (n = 106 [35.1%]), and high D-dimer levels (median [interquartile range]: 608 [523;707] ng/mL). The mortality rate in this group was high (n = 63 [20.9%]). Multivariable logistic regression, the Cox proportional hazards, and Kaplan-Meier models revealed that the use of therapeutic anticoagulation agents affected the risk of all-cause cumulative mortality.
CONCLUSION: Age, hypertension, pneumonia, therapeutic anticoagulation, and methylprednisolone use were found to be strong predictors of in-hospital mortality. In elderly hypertensive COVID-19 patients on therapeutic anticoagulation were found to have 2.3 times higher risk of in-hospital mortality. All cause in-hospital mortality rate in the therapeutic anticoagulation group was up to 21%.
METHODS: Patients were stratified based on ferritin levels (ferritin levels ≤ 1000 or >1000).
RESULTS: Approximately 89% (118) of the patients with ferritin levels > 1000 had pneumonia, and 51% (67) had hypertension. Fever (97, 73.5%) and shortness of breath (80, 61%) were two major symptoms among the patients in this group. Logistic regression analysis indicated that ferritin level (odds ratio [OR] = 0.36, 95% confidence interval [CI] = 0.21-0.62; p 1000.
CONCLUSION: In this study, higher levels of serum ferritin were found to be an independent predictor of in-hоsрitаl mоrtаlity.