Abstract Cobalt catalyzed coupling of styrenes with a variety of activated organic bromides such as α‐bromoesters, α‐bromoamides, and α‐bromoketones is studied in the presence of tBuOOH as the oxidant.
The 1-year mortality and health consequences of COVID-19 in cancer patients are relatively underexplored. In this multicenter cohort study, 166 COVID-19 patients with cancer were compared with 498 non-cancer COVID-19 patients and 498 non-COVID cancer patients. The 1-year all-cause mortality and hospital mortality rates in Cancer COVID-19 Cohort (30% and 20%) were significantly higher than those in COVID-19 Cohort (9% and 8%, both P < .001) and Cancer Cohort (16% and 2%, both P < 0.001). The 12-month all-cause post-discharge mortality rate in survival discharged Cancer COVID-19 Cohort (8%) was higher than that in COVID-19 Cohort (0.4%, P < .001) but similar to that in Cancer Cohort (15%, P = .084). The incidence of sequelae in Cancer COVID-19 Cohort (23%, 26/114) is similar to that in COVID-19 Cohort (30%, 130/432, P = .13). The 1-year all-cause mortality was high among patients with hematologic malignancies (59%), followed by those who have nasopharyngeal, brain, and skin tumors (45%), digestive system neoplasm (43%), and lung cancers (32%). The rate was moderate among patients with genitourinary (14%), female genital (13%), breast (11%), and thyroid tumors (0). COVID-19 patients with cancer showed a high rate of in-hospital mortality and 1-year all-cause mortality, but the 12-month all-cause post-discharge mortality rate in survival discharged cancer COVID-19 patients was similar to that in Cancer Cohort. Comparing to COVID-19 Cohort, risk stratification showed that hematologic, nasopharyngeal, brain, digestive system, and lung tumors were high risk (44% vs 9%, P < 0.001), while genitourinary, female genital, breast, and thyroid tumors had moderate risk (10% vs 9%, P = .85) in COVID-19 Cancer Cohort. Different tumor subtypes had different effects on COVID-19. But if cancer patients with COVID-19 manage to survive their COVID-19 infections, then long-term mortality appears to be similar to the cancer patients without COVID-19, and their long-term clinical sequelae were similar to the COVID-19 patients without cancer.
Regenerative therapies based on mesenchymal stem cells (MSCs) show promise in treating a wide range of disorders. However, the replicative senescence of MSCs during in vitro expansion poses a challenge to obtaining a substantial quantity of high-quality MSCs. In this investigation, a piezoelectric β-poly(vinylidene fluoride) film-based culture plate (β-CP) was developed with an antisenescence effect on cultured human umbilical cord-derived MSCs. Compared to traditional tissue culture plates (TCPs) and α-poly(vinylidene fluoride) film-based culture plates, the senescence markers of p21, p53, interleukin-6 and insulin-like growth factor-binding protein-7, stemness markers of OCT4 and NANOG, and telomere length of MSCs cultured on β-CPs were significantly improved. Additionally, MSCs at passage 18 cultured on β-CPs showed significantly better multipotency and pro-angiogenic capacities in vitro, and higher wound healing abilities in a mouse model. Mechanistically, β-CPs rejuvenated senescent MSCs by improving mitochondrial functions and mitigating oxidative and glycoxidative stresses. Overall, this study presents β-CPs as a promising approach for efficient and straightforward antisenescence expansion of MSCs while preserving their stemness, thereby holding great potential for large-scale production of MSCs for clinical application in cell therapies.
Objective:To establish a multi-drug resistance(MDR) cell line Jurkat/Doxorubicin(DOX) derived from human T lymphocyte leukemia cell line Jurkat,and to compare the biological characteristics between Jurkat/DOX and Jurkat cell line.Methods:Jurkat cells were induced with long-term,singular,and dose-increasing DOX addition to MDR cell line Jurkat/DOX.The biological characteristics and the spectrum of MDR of Jurkat/DOX were evaluated by MTT assay.The intracellular accumulation of DOX was detected by flow cytometer and laser scanning confocal microscope.The expression of mdr1 was analyzed by RT-PCR.Western blot was also performed to detect the expression of P-gp.Results:MDR cell line Jurkat/DOX was established by long-term,intermittent,singular and dose-increasing DOX induction.The growth of Jurkat/DOX was slower than that in Jurkat cell line.Jurkat/DOX cells were resistant not only to the original DOX,but also to many other anticancer drugs such as CTX,VCR,and DNR.Intracellular accumulation of DOX was significantly less than that in parent cells.The expression of mdr1 gene and P-gp protein were up-regulated in Jurkat/DOX cell line.Conclusion:The MDR cell line Jurkat/DOX was successfully established,it has the property of resistant to many anticancer drugs,and the resistant maybe closely related to the over-expression of P-gp.
Abstract Background: We recently reported that transplantation of autologous bone marrow mononuclear cells (BM-MNCs) may be an effective and promising therapy to treat refractory diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM). This study was designed to investigate the potential mechanisms of BM-MNCs therapy.Methods: This clinical study recruited 60 patients with DPN, 30 T2DM patients without complications, 30 healthy control participants. All clinical parameters, the levels of inflammatory markers and growth factors in three groups were compared. All patients with DPN received one intramuscular injection of BM-MNCs and clinical follow-ups after the therapy for 2 days, 1, 4, 12, 24, and 48 weeks. Then they were divided into the responder and non-responder groups based on the improvement of nerve conduction velocity. Binary logistic regression was performed to evaluate the corresponding prognostic factors for BM-MNCs treatment.Results: Patients in DPN group had higher level of tumor necrosis factor-α (TNF-α) and lower level of vascular endothelial growth factor (VEGF) than those in control group. DPN group had the highest level of soluble intercellular adhesion molecule-1 (sICAM-1) among three groups. The level of nerve growth factor (NGF) in DPN group was slightly lower than that in DM group. Neuropathic symptoms were significantly improved after BM-MNCs injection. Thirty five of 54 patients with DPN (64.8%) reached the primary endpoint, and were regarded as the responders. Compared to non-responders, responders were younger, had a longer history of diabetes, and had higher numbers of mobilized CD34+ cells and BM-MNCs. The levels of TNF-α and sICAM-1 decreased just after BM-MNCs injection in both groups and slowly reverted to baseline levels. The durations of downtrend of TNF-α and sICAM-1 in responder group lasted longer than that in non-responder group. Serum level of VEGF in responder group increased immediately after BM-MNC therapy, and reached the highest point after the injection for 12 weeks. On the other hand, VEGF levels in the non-responder group only increased slightly. The number of applied CD34+ cells (OR=1.567, 95% CI 1.106-2.222, p=0.012) and duration of diabetes (OR=0.760, 95% CI 0.597-0.967, p=0.025) were the independent predictors of responding to BM-MNCs therapy. No adverse event associated with the treatment was observed during follow-up observations.Conclusions: BM-MNCs transplantation is an effective and promising therapeutic strategy to treat refractory DPN. The immune regulation and paracrine function of BM-MNCs may contribute to the improvement of DPN.
The objective of this study was to evaluate whether combinations of sulbactam, meropenem, and polymyxin-B could reduce or close the gap of mutant selection window (MSW) of individual antibiotics against Acinetobacter baumannii harboring OXA-23. MICs of three antimicrobials used alone and in combination (meropenem/polymyxin-B or meropenem/polymyxin-B/sulbactam) were obtained in 11 clinical isolates and mutant prevention concentrations were determined in 4 of the 11 isolates. All isolates were resistant to meropenem or polymyxin-B. Combining meropenem and polymyxin-B with or without sulbactam resulted in synergistic bactericidal activities. Pharmacokinetic (PK) simulations of drug concentrations in the blood and epithelial lining fluid coupled with pharmacodynamic (PD) evaluations revealed that the fractions of time over the 24-h in terms of free drug concentration within the MSW (fTMSW) and above the MPC (fT>MPC) were optimized by combination therapy. The resultant clinical regimens of meropenem, polymyxin-B, and sulbactam evaluated in the PK-PD analysis were 2 g q8h, 2.5 mg/kg loading dose followed by 1.5 mg/kg q12h, and 3 g q8h, respectively, in patients with normal renal function. Subsequent corresponding equivalent exposure regimens would depend on the extent of renal failure. The overall results indicate that combination antibiotics consisting of sulbactam/meropenem/polymyxin-B can confer potential efficacy against A. baumannii harboring OXA-23, and reduce the opportunity for bacteria to develop further resistance. This study provides a framework for pharmacodynamic evaluation of drug-resistant mutant suppression in an antimicrobial co-administration setting. The results thereby lay the groundwork for additional studies and future clinical confirmation is warranted.
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