Hepatocellular carcinoma (HCC), one of the most common and deadliest malignancies worldwide, has a poor prognosis, owing to its high potential for vascular invasion and metastasis and the lack of ...biomarkers for early diagnosis. Thus, it must be a crucial factor for investigating therapeutic strategies for HCC to identify the functional molecular targets. Here, we reported a novel chemokine, CKLF1, that might act as a pivotal modulator in the invasion and metastasis of HCC and could serve as an attractive target for cancer therapy.
Bioinformatics analysis, PCR, Western blotting, and IHC were performed to detect the expression of CKLF1 in HCC. The function of CKLF1 was demonstrated by a series of
and
experiments. Pharmacologic treatment, flow cytometry, and Western blotting were carried out to demonstrate the potential mechanisms of CKLF1.
We proved that CKLF1 was overexpressed in HCC tissues and was related to tumor stage, vascular invasion, and patient survival. Then, functional assays showed that CKLF1 promoted hepatocellular carcinogenesis and metastatic potential. Finally, the IL6/STAT3 signaling pathway was involved in the mechanistic investigation. The results demonstrated that CKLF1 enhanced the progression of HCC and prevented doxorubicin-induced apoptosis through activating the IL6/STAT3 pathway.
These data showed that CKLF1 inhibited apoptosis and promoted malignant transformation through the IL6/STAT3 pathway, and ultimately enhanced the development and metastasis of HCC. Thus, our work revealed that CKLF1 was a significant prognostic factor of HCC and might be a potential molecular therapeutic target for HCC.
Highly efficient: The title reaction provides biologically interesting chiral trifluoromethyl dihydroquinazolinone frameworks in high yields (up to 97 %) and with high enantioselectivities (up to 98 ...% ee), using as low as 1 mol % of catalyst (see scheme). Moreover, anti‐HIV drug candidate DPC 083 was efficiently synthesized using the highly enantioselective aza‐Henry reaction as a key step.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Purpose
Identify how early COVID-19 public health messages incorporated in the tenets of the extended parallel process model (EPPM).
Setting
YouTube videos developed by governmental departments, ...medical institutions, news organizations, and non-profit organizations in the United States were aggregated.
Method
This qualitative study conducted a keyword search to identify public service announcements (PSAs). The sample was further refined after searching PSAs that contained fear appeals. A thematic analysis was performed by using the constant comparative method.
Sample
A total of forty-three videos was included in the final analysis.
Result
Two themes emerged regarding messages aimed at arousing the perceived severity of threat. These themes include emphasizing the consequences of being infected and utilizing personal narratives. Perceived susceptibility of threat was aroused by emphasizing that some groups have higher risks than others. Two themes emerged around arousing perceived response efficacy: (1) the authority of professionals; and (2) altruism and personal responsibility. One way was identified to arouse perceived self-efficacy, which is informing the protective measures.
Conclusion
Multiple strategies were used in PSAs about COVID-19 to arouse fear during the early stages of the pandemic. The utilization of self-efficacy was oversimplified, by not providing details about the rationale for the recommended behavior.
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FSPLJ, NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Human endogenous retrovirus (HERVs), originating from exogenous retroviral infections of germ cells millions of years ago, have the potential for human diseases. Syncytin-1, an envelope protein ...encoded by the HERV W family, participates in the contexts of schizophrenia, multiple sclerosis, diabetes, and several types of cancers. Nevertheless, there is no report on the expression pattern and potential mechanism of Syncytin-1 in HCC. Here we found Syncytin-1 expression was up-regulated in HCC compared to adjacent non-tumorous tissues, especially in advanced HCC. Syncytin-1 was an independent risk factor to predict vascular invasion, metastasis, larger tumor size, and poor prognosis in HCC patients. Further analysis discovered that Syncytin-1 overexpression positively associated with HCC patients with serum HBsAg positive. Functional experiments in vitro and in vivo demonstrated that Syncytin-1 enhanced cell proliferation, metastasis, and tumorigenicity in HCC. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that the mitogen-activated protein kinase (MEK)/extracellular signal-regulated protein kinase (ERK) pathway was involved in HCC. Our clinical data indicated that the levels of phosphorylation MEK1/2 and ERK1/2 were increased in HCC comparing with adjacent non-tumorous tissues. It showed the linear correlation between Syncytin-1 expression and upregulated MEK1/2 and ERK1/2 phosphorylation levels in HCC. Furthermore, Syncytin-1 activated MEK/ERK pathway in HCC cells. In-depth research showed that the inflammation-activated MEK/ERK pathway was essential in Syncytin-1 promoted hepatocarcinogenesis. Syncytin-1 suppressed doxorubicin-induced apoptosis via MEK/ERK cascade. In conclusion, Syncytin-1 promoted HCC progression and doxorubicin resistance via the inflammation-activated MEK/ERK pathway. Our findings revealed that Syncytin-1 was a potential prognostic biomarker and therapeutic target for HCC.
A novel method for organocatalytic oxidation through oxidative enamine catalysis was developed with excellent compatibility for the direct syntheses of enals from simple saturated alcohols. By using ...this amine-catalyzed IBX-oxidation, a wide range of aromatic and aliphatic substituted enals were successfully generated in high yields and exclusively stereoselective E-geometry. Moreover, varying the solvents and/or the loading amounts of IBX allowed for the selective oxidation of alcohols and aldehydes. Importantly, the homologous application of this method provided a selective and efficient way of preparing various highly sensitive conjugated polyene frameworks, which are enriched in natural products.
An organocatalytic enantioselective addition reaction of cyclic ketoimines with phosphites has been developed for the first time. The process, catalyzed by Soós' quinine thiourea, affords ...synthetically and medicinally interesting enantioenriched trifluoromethyl dihydroquinazolinones in high yields and with high enantioselectivities.
The coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was identified in December 2019 and has subsequently spread worldwide. Currently, there ...is no effective method to cure COVID‐19. Mesenchymal stromal cells (MSCs) may be able to effectively treat COVID‐19, especially for severe and critical patients. Menstrual blood‐derived MSCs have recently received much attention due to their superior proliferation ability and their lack of ethical problems. Forty‐four patients were enrolled from January to April 2020 in a multicenter, open‐label, nonrandomized, parallel‐controlled exploratory trial. Twenty‐six patients received allogeneic, menstrual blood‐derived MSC therapy, and concomitant medications (experimental group), and 18 patients received only concomitant medications (control group). The experimental group was treated with three infusions totaling 9 × 107 MSCs, one infusion every other day. Primary and secondary endpoints related to safety and efficacy were assessed at various time points during the 1‐month period following MSC infusion. Safety was measured using the frequency of treatment‐related adverse events (AEs). Patients in the MSC group showed significantly lower mortality (7.69% died in the experimental group vs 33.33% in the control group; P = .048). There was a significant improvement in dyspnea while undergoing MSC infusion on days 1, 3, and 5. Additionally, SpO2 was significantly improved following MSC infusion, and chest imaging results were improved in the experimental group in the first month after MSC infusion. The incidence of most AEs did not differ between the groups. MSC‐based therapy may serve as a promising alternative method for treating severe and critical COVID‐19.
Menstrual blood‐derived MSC transplantation significantly lowers the mortality of severe and critical SARS‐CoV‐2‐induced COVID‐19.
This prospective and systematic report assessed the ability of menstrual blood‐derived MSCs to treat both severe and critically ill COVID‐19 patients.
MSC‐based therapy may serve in future clinical applications as an alternative way for the treatment of COVID‐19
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This study aimed to investigate two types of corneal flap thickness on opaque bubble layer (OBL) formation in Visumax femtosecond laser-assisted stromal for situ keratomileusis (FS-LASIK).
This ...retrospective study analyzed 203 eyes of 103 patients (32 men and 71 women) who underwent Visumax FS-LASIK between January 2020 and June 2020, and according to corneal flap thickness, they were divided into the 100-μm group (64 eyes) and the 110-μm group (139 eyes). Anterior-segment examination revealed no abnormal findings. Preoperatively, intraocular pressure (IOP), central corneal thickness (CCT), residual stromal thickness (RST), spherical power, cylindrical power, flat keratometry (K1), steep keratometry (K2), and biomechanical parameters including deformation amplitude (DA) ratio, Integrated Radius, stiffness parameter at first applanation (SP-A1), and Ambrosio relational thickness to the horizontal profile (ARTh) were evaluated. Primary outcomes were the incidence of OBL formation in the two groups compared by the Chi-square test and the correlation between the incidence of OBL and the above preoperative data by Spearman's Rho test. Secondary outcomes were the comparisons corrected by the generalized estimating equation (GEE) model.
The incidence of OBL formation in the 100-μm group was 59.4 %, which was higher than that in the 110-μm group (23.0 %) with a significant difference (χ2 = 25.635, P < 0.001). The thinner corneal flap thickness (r = −0.355, P < 0.001) and higher spherical power (r = −0.142, P < 0.05) correlated with OBL formation. Higher K1 (r = 0.217, P < 0.01) and K2 (r = 0.198, P < 0.01) also correlated with OBL formation. The results of the GEE correction analysis showed higher rates of OBL formation in the 100-μm group (odds ratio OR = 4.704, 95 % CI 1.681–13.161, P < 0.01).
OBL was more likely to occur with the 100-μm corneal flap than with the 110-μm corneal flap in Visumax FS-LASIK. The risk of OBL formation in the 100-μm group was 4.704 times higher than that in the 110-μm group.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
BACKGROUND The novel severe acute respiratory syndrome coronavirus 2 threatens human health, and the mortality rate is higher in patients who develop myocardial damage. However, the possible risk ...factors for myocardial damage in patients with coronavirus disease 2019 (COVID-19) are not fully known. METHODS AND RESULTS Critical type patients were selected randomly from 204 confirmed COVID-19 cases occurring in Renmin Hospital of Wuhan University from February 1, 2020 to February 24, 2020. Univariate analyses were used to compare the 2 groups: the myocardial damage group and the non-myocardial damage group. A total of 82 critical patients with COVID-19 were recruited: 34 with myocardial damage and 48 without myocardial damage. A total of 30 patients died in the myocardial damage group, and 20 died in the non-myocardial damage group. In univariate analysis, the proportion of elderly patients (>70 years old, 70.59% versus 37.50%;
=0.003) and patients with cardiovascular disease (41.18% versus 12.50%;
=0.003) was higher among myocardial damage patients than among non-myocardial damage patients. Multivariate analysis showed that age >70 years old (hazard ratio HR, 2.44; 95% CI, 1.01-5.40), CRP (C-reactive protein) >100 mg/L (HR, 1.92; 95% CI, 0.94-3.92), lactate dehydrogenase >300 U/L (HR, 2.67; 95% CI, 1.03-6.90), and lactic acid >3 mmol/L (HR, 3.25; 95% CI, 1.57-6.75) were independent risk factors for myocardial damage in patients with COVID-19. CONCLUSIONS Old age (>70 years old), CRP >100 mg/L, lactate dehydrogenase >300 U/L, and lactic acid >3 mmol/L are high-risk factors related to myocardial damage in critical patients with COVID-19.
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