Immunogenicity and safety of boosting with a recombinant two-component SARS-CoV-2 vaccine: two randomized, parallel-controlled, phase 2 studies.

BACKGROUND: Recombinant protein vaccines are vital for broad protection against SARS-CoV-2 variants. This study assessed ReCOV as a booster in two Phase 2 trials. RESEARCH DESIGN AND METHODS: Study-1 involved subjects were randomized (1:1:1) to receive 20 µg ReCOV, 40 µg ReCOV, or an inactivated vaccine (COVILO®) in the United Arab Emirates. Study-2 participating individuals were randomized (1:1:1) to receive 20 µg ReCOV (pilot batch, ReCOV HA), 20 µg ReCOV (commercial batch, ReCOV TC), or 30 µg BNT162b2 (COMIRNATY®) in the Philippines. The primary immunogenicity objectives was to compare the geometric mean titer (GMT) and seroconversion rate (SCR) of neutralizing antibodies induced by one ReCOV booster dose with those of inactivated vaccine and BNT162b2, respectively, at 14 days post-booster. RESULTS: Heterologous ReCOV booster doses were safe and induced comparable immune responses to inactivated vaccines and BNT162b2 against Omicron variants and the prototype. They showed significant advantages in cross-neutralization against multiple SARS-CoV-2 variants, surpassing inactivated vaccines and BNT162b2, with good immune persistence. CONCLUSIONS: Heterologous ReCOV boosting was safe and effective, showing promise in combating COVID-19. The study highlights ReCOV's potential for enhanced protection, supported by strong cross-neutralization and immune persistence. CLINICAL TRIAL REGISTRATION: Study-1, www.clinicaltrials.gov, identifier is NCT05323435; Study-2, www.clinicaltrials.gov, identifier is NCT05084989.

Effect of ilexonin A on proliferation and migration of bone mesenchymal stem cells in rats / 中国药理学通报

Aim To observe the effect of ilexonin A (IA) on the proliferation of bone marrow mesenchymal stem cells(BMSCs),and to investigate whether IA can promote the migration of BMSCs by up-regulating the expression of CXCR4 in rats. Methods MTT method was used to assay and analyse the proliferation of BM-SCs which were pretreated with different concentrations of IA (3.125,6.25,12.5,25,50,100,200,400, 800 mg·L-1) for 24,48 and 72h,then the best con-centration and the best optimum time were screened. The third generation of BMSCs was exposed to the opti-mal concentration of IA for 48h. The Transwell system was used to carry out the experiment of BMSCs migra-tion. Western blot was used to analyse the expression of CXCR4. Results MTT assay showed that com-pared with control group, the proliferation of BMSCs was significantly reduced in IA 100 ~800 mg·L-1 groups at 24h(P < 0.05); compared with control group, the proliferation of BMSCs significantly de-creased in IA 100~800 mg·L-1groups at 48h(P<0.05),but markedly increased in IA 6.25 and 3.125 mg·L-1groups (P <0.05); compared with control group,the proliferation of BMSCs was significantly re-duced in IA 12.5~800 mg·L-1groups at 72h(P<0.05). The above results indicated that the BMSCs in-cubated with IA 6.25 and 3.125 mg·L-1for 48h were the optimal choice to promote proliferation. The Transwell migration assay showed that incubation with IA 6.25 and 3.125 mg·L-1for 48h could significant-ly increase the migration of BMSCs(P <0.05), and the migration rate was not related with the concentra-tion of IA. This effect was completely blocked by AMD3100(the antagonist of CXCR4). Western blot showed that incubation with IA 6.25 and 3.125 mg· L-1for 48h could increase the expression of CXCR4 in BMSCs(P<0.05). Conclusion IA can promote the proliferation of BMSCs and increase the migration of BMSCs by up-regulating the expression of CXCR4.

Generation of a new strain of NOD/SCID/IL2Rγ mice with targeted disruption of Prkdc and IL2Rγ genes using CRISPR/Cas9 system / 南方医科大学学报

<p><b>OBJECTIVE</b>The NOD/SCID/IL2Rγ (NSG) mouse strain is the most widely used immunodeficient strain for xenograft transplantation. However, the existing SCID mutation is a spontaneous mutation of the Prkdc gene, which leads to leaky T cell developmental block and difficulty in genotyping. It is therefore important to develop a new strain of NSG mice with targeted disruption of Prkdc and IL2Rγ genes.</p><p><b>METHODS</b>Targeted disruption of Prkdc and IL2Rγ genes was achieved using the CRISPR/Cas9 system. By intercrossing the knockout and NOD mice, we obtained a novel strain of NOD/SCID/IL2Rγ(NSG) mice, denoted as cNSG (Chinese NSG) mice.</p><p><b>RESULTS</b>In addition to the NOD mutation, cNSG mice exhibited a complete absence of T cells, B cells and NK cells. cNSG mice allowed more efficient engraftment of human cancer cells than the commonly used immunodeficient nude mice.</p><p><b>CONCLUSION</b>cNSG mice will provide an important xenotransplantation model for biomedical research.</p>

Fire-needle therapy for deglutition disorders in post-stroke pseudobulbar palsy:a randomized controlled trial / 针灸推拿医学（英文版）

Objective:To observe the clinical efficacy of fire-needle therapy in treating deglutition disorders due to pseudobulbar palsy in the remission stage of stroke.Methods:Sixty-two eligible subjects were divided into a fire-needle group and a rehabilitation group by a simple randomization method at a ratio of 1:1.The two groups received same basic intervention;in addition,the fire-needle group received fire-needle treatment,while the rehabilitation group received rehabilitation training.The two groups of subjects all received a 3-week treatment and were evaluated by the dysphagia severity rating scale (DSRS),modified Mann assessment of swallow ability (MMASA) and Kubota Toshio swallow test (KTST) before and after the intervention.The complications and adverse events occurred during the trial were recorded.The data were statistically analyzed.Results:At the third week,the DSRS,MMASA and KTST scores changed significantly compared with the baseline in both groups (P＜0.05),and the changes in the fire-needle group were more significant than those in the rehabilitation group (P＜0.05).The between-group comparison at the third week showed that the therapeutic efficacy in the fire-needle group was superior to that in the rehabilitation group (P＜0.05).Conclusion:Fire-needle therapy can obviously change the DSRS,MMASA and KTST scores in pseudobulbar palsy in the remission stage of stroke,and significantly enhance the therapeutic efficacy of the treatment of deglutition disorders in this stage.

DNA damage effects on human skin keratinocytes induced by sulphur mustard / 军事医学

Objective To investigate the toxic effects and mechanisms of sulphur mustard on DNA damage of human immortalized epidermal keratinocytes (HacaT cells).Methods The inhibitory effect of sulphur mustard on the proliferation of HacaT cells was detected by CCK-8 method.The apoptosis index of cells was measured by Annexin V-FITC method.The effects of sulphur mustard on DNA damage were detected by single cell gel electrophoresis.The expression levels of DNA damage and repair related proteins were detected by Western blot.Results The proliferation rate of HacaT cells was inhibited in a dose-dependent manner after treatment with sulphur mustard for 24 h (IC50 value was 121 mol/L).The apoptotic and comet tailing rates of cells treated with sulphur mustard also increased in a dose-dependent manner.The expression levels of DNA damage and repair related proteins were changed after treatment with sulphur mustard.Conclusion Sulphur mustard has significant cytotoxic effect on HacaT cells,and can induce apoptosis and DNA damage.In addition,ATM-P53-γH2AX-PARP signaling pathway plays an important role in the repair of DNA damage induced by sulphur mustard.

Iso-suillin from Suillus flavus Induces Apoptosis in Human Small Cell Lung Cancer H446 Cell Line / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The suillin isoform iso-suillin is a natural substance isolated from a petroleum ether extract of the fruiting bodies of the mushroom Suillus flavus. Previous studies have found its inhibition effect on some cancer cells, and we aimed to study its effects on human small cell lung cancer H446 cell line.</p><p><b>METHODS</b>Cell viability was measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Cellular morphological changes (apoptosis and necrosis) were evaluated using an electron microscope and Hoechst 33258 staining detected by the inverted microscope. Flow cytometry was used to detect cell apoptosis, cell cycle distribution, and mitochondrial membrane potential. Protein expression was determined by Western blotting analysis.</p><p><b>RESULTS</b>Here, we describe the ability of iso-suillin to inhibit the growth of H446 cells in time- and dose-dependent way. Iso-suillin had no obvious impact on normal human lymphocyte proliferation at low concentrations (9.09, 18.17, or 36.35 μmol/L) but promoted lymphocyte proliferation at a high concentration (72.70 μmol/L). After treatment of different concentrations of iso-suillin (6.82, 13.63, or 20.45 μmol/L), the apoptosis rate of H446 cells increased with increasing concentrations of iso-suillin (16.70%, 35.54%, and 49.20%, respectively, all P < 0.05 compared with the control), and the expression of related apoptotic proteins in the mitochondrial pathway including cytochrome c and caspase-9 were up-regulated compared with the control (all P < 0.05). On the contrary, Bcl-2/Bax ratio was down-regulated compared with the control. Besides, the expression of pro-apoptotic proteins in the death receptor apoptosis pathway, including Fas-associating protein with a novel death domain and caspase-8, and the expression of caspase-3, a downstream regulatory protein of apoptosis, were also increased compared with the control (all P < 0.05). Inhibitors of caspase-9 and caspase-8 reversed the apoptosis process in H446 cells to varying degrees.</p><p><b>CONCLUSIONS</b>These results suggest that iso-suillin could induce H446 cell apoptosis through the mitochondrial pathway and the death-receptor pathway. Therefore, iso-suillin might have a potential application as a novel drug for lung cancer treatment.</p>