Tobacco smoking confers risk for severe COVID-19 unexplainable by pulmonary imaging.

BACKGROUND: COVID-19 is a new pneumonia. It has been hypothesized that tobacco smoking history may increase severity of this disease in the patients once infected by the underlying coronavirus SARS-CoV-2 because smoking and COVID-19 both cause lung damage. However, this hypothesis has not been tested. OBJECTIVE: Current study was designed to focus on smoking history in patients with COVID-19 and test this hypothesis that tobacco smoking history increases risk for severe COVID-19 by damaging the lungs. METHODS AND RESULTS: This was a single-site, retrospective case series study of clinical associations, between epidemiological findings and clinical manifestations, radiographical or laboratory results. In our well-characterized cohort of 954 patients including 56 with tobacco smoking history, smoking history increased the risk for severe COVID-19 with an odds ratio (OR) of 5.5 (95% CI: 3.1-9.9; P = 7.3 × 10-8 ). Meta-analysis of ten cohorts for 2891 patients together obtained an OR of 2.5 (95% CI: 1.9-3.3; P < 0.00001). Semi-quantitative analysis of lung images for each of five lobes revealed a significant difference in neither lung damage at first examination nor dynamics of the lung damage at different time-points of examinations between the smoking and nonsmoking groups. No significant differences were found either in laboratory results including D-dimer and C-reactive protein levels except different covariances for density of the immune cells lymphocyte (P = 3.8 × 10-64 ) and neutrophil (P = 3.9 × 10-46 ). CONCLUSION: Tobacco smoking history increases the risk for great severity of COVID-19 but this risk is achieved unlikely by affecting the lungs.

Relationship between methylation status of RASSF2A gene promoter and endometriosis-associated ovarian cancer.

Relationship between the methylation status of the RASSF2A gene promoter and endometriosis-associated ovarian cancer (EAOC) was explored. Between January 2013 and January 2016, tissue samples were collected from 30 patients diagnosed with ovarian endometriosis cyst (EC group), 30 patients diagnosed with ovarian endometrial adenocarcinoma (OEA group) and 30 patients diagnosed with ovarian clear cell carcinoma (OCC group). Additionally, 30 cases of normal endometrium tissues were collected for the control group. The methylation status of the RASSF2A promoter was evaluated by combined bisulfite restriction enzyme analysis (COBRA). RT-PCR was used to detect the expression level of RASSF2A mRNA in tissues. Relationship between methylation status and RASSF2A mRNA expression level and the patient age, tumor clinical stage, tumor grading and pathological type were analyzed. Results showed that in the OEA and OCC groups, the methylation degrees of the RASSF2A promoter were obviously higher than that of the other two groups. The expression level of RASSF2A mRNA in the OEA and OCC groups was lower than that of the other two groups. The methylation degree of the RASSF2A promoter was related to clinical staging and grading. No relationship between the methylation degree of the RASSF2A promoter and patient’s age and the pathological type of the tissue was detected. We concluded that the methylation status of the RASSF2A gene promoter could be considered an excellent indicator for early detection of ovarian cancers.

Puerarin protects dopaminergic neurons in Parkinson's disease models.

It has been acknowledged that oxidative stress, resulting in the apoptosis of dopaminergic neurons, is a key mechanism in the pathogenesis of Parkinson's disease (PD). Puerarin, extracted from the root of pueraria lobata, has been clinically used for ischemic heart disease and cerebrovascular diseases as an oxygen free radical scavenger. In this study, we aimed to explore the effect of puerarin on dopaminergic cell degeneration in vitro and in vivo and its possible underlying mechanisms. In SH-SY5Y cells, the reduction of cell viability, apoptosis rate and average DCFH-DA fluorescence intensity of puerarin-treated (0, 10, 50, 100 and 150 µM) cells were significantly lower than control group. In rotenone-based rodent models, puerarin treatment for 7 days ameliorated apomorphine-induced rotations significantly in Pue-50 and Pue-100 group by 45.65% and 53.06% in the first week, by 44.60% and 48.45% in the second week. Moreover, compared to control group, puerarin increased tyrosine hydroxylase (TH) expression in the substantia nigra by 85.52% and 84.26% in Pue-50 group and Pue-100 group, and upregulated the vesicular monoamine transporter 2 (VMAT2) by 41.24% in Pue-50 group and 35.20% in Pue-100 group, and decreased ubiquitin expression by 47.55% in Pue-50 group and 69.15% in Pue-100 group. These data indicated that puerarin alleviated the oxidative stress and apoptosis in a PD cellular model, protected the dopaminergic neurons against rotenone toxicity and decreased the abnormal protein overexpressing in PD animal models. These findings suggest that puerarin may develop into a neuroprotective alternative for patients with PD.

Potential autophagy enhancers attenuate rotenone-induced toxicity in SH-SY5Y.

Recent studies have shown that autophagy upregulation may be a tractable therapeutic intervention for clearing the disease-causing proteins, including α-synuclein, ubiquitin, and other misfolded or aggregated proteins in Parkinson's disease (PD). In this study, we explored a novel pharmacotherapeutic approach to treating PD by utilizing potential autophagy enhancers valproic acid (VPA) and carbamazepine (CBZ). Pretreatment with VPA (3 mM) and CBZ (50 µM) along with positive control rapamycin (Rap, 0.2 µM) or lithium (LiCl, 10 mM) significantly enhanced cell viability, decreased rotenone-induced nuclear fragmentation and apoptosis, ameliorated the decrease in mitochondrial membrane potential, reduced reactive oxygen species generation in the human neuroblastoma SH-SY5Y cells. Specifically, the numbers of lysosomes and autophagic vacuolar organelles were increased and the microtubule-associated protein 1 light chain 3-II (LC3-II) expression was up-regulated by VPA, CBZ, Rap, and LiCl (53%, 31%, 72%, and 63%), suggesting that these agents activated autophagic pathways. Moreover, pretreatment with the autophagy inhibitor chloroquine (Chl, 10 µM) remarkably strengthened rotenone toxicity in these cells. Our results suggest that VPA and CBZ, the most commonly used anti-epilepsy and mood-stabilizing medications with low-risk and easy administration might be potential therapeutics for PD.

Glyceraldehyde-3-phosphate dehydrogenase: activity inhibition and protein overexpression in rotenone models for Parkinson's disease.

Rotenone, a widely used pesticide and an environmental risk factor for Parkinson's disease (PD), induces nigrostriatal injury, Lewy body-like inclusions, and Parkinsonian symptoms in rat models for PD. Our previous data indicated that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) overexpression and glycolytic inhibition were co-current in rotenone-induced PC12 (rat adrenal pheochromocytoma cells) cell death. However, whether GAPDH overexpression plays any role in dopaminergic neurodegeneration in vivo remains unknown. In this study, we have found that GAPDH overexpression and GAPDH-positive Lewy body-like aggregates in nigral dopaminergic neurons while nigral GAPDH glycolytic activity decreases in rotenone-based PD animal models. Furthermore, GAPDH knockdown reduces rotenone toxicity significantly in PC12. These in vitro and in vivo data suggest that GAPDH contributes to the pathogenesis of Parkinson's disease, possibly representing a new molecular target for neuroprotective strategies and alternative therapies for PD.

VEGF-expressing human umbilical cord mesenchymal stem cells, an improved therapy strategy for Parkinson's disease.

The umbilical cord provides a rich source of primitive mesenchymal stem cells (human umbilical cord mesenchymal stem cells (HUMSCs)), which have the potential for transplantation-based treatments of Parkinson's Disease (PD). Our pervious study indicated that adenovirus-associated virus-mediated intrastriatal delivery of human vascular endothelial growth factor 165 (VEGF 165) conferred molecular protection to the dopaminergic system. As both VEGF and HUMSCs displayed limited neuroprotection, in this study we investigated whether HUMSCs combined with VEGF expression could offer enhanced neuroprotection. HUMSCs were modified by adenovirus-mediated VEGF gene transfer, and subsequently transplanted into rotenone-lesioned striatum of hemiparkinsonian rats. As a result, HUMSCs differentiated into dopaminergic neuron-like cells on the basis of neuron-specific enolase (NSE) (neuronal marker), glial fibrillary acidic protein (GFAP) (astrocyte marker), nestin (neural stem cell marker) and tyrosine hydroxylase (TH) (dopaminergic marker) expression. Further, VEGF expression significantly enhanced the dopaminergic differentiation of HUMSCs in vivo. HUMSC transplantation ameliorated apomorphine-evoked rotations and reduced the loss of dopaminergic neurons in the lesioned substantia nigra (SNc), which was enhanced significantly by VEGF expression in HUMSCs. These findings present the suitability of HUMSC as a vector for gene therapy and suggest that stem cell engineering with VEGF may improve the transplantation strategy for the treatment of PD.

Platelet immunoregulatory factors.

A number of soluble and membrane-associated proteins are known to mediate platelet:leukocyte interactions. Platelet-derived factors that have attracted the most attention to date include transforming growth factor beta, interleukin 1 and platelet factor 4. Recently, we have uncovered another protein within platelets that has leukocyte modulatory activity. It was previously characterized as an endometrial glycoprotein named placental protein 14 (PP14) with suppressive effects upon lymphocyte proliferation, pro-inflammatory cytokine production and natural killer cell function. The "hematopoietic" PP14 derived from cells of the megakaryocytic lineage shares this immunosuppressive property, as evaluated by two-way mixed lymphocyte cultures. Interestingly, two alternatively spliced hematopoietic PP14 mRNAs have been cloned which differ in their encoded proteins. Cell-free translation and transfection analyses have verified the translatability of both PP14 mRNA species and allowed for the analysis of their glycosylation properties. PP14, a member of the lipocalin structural superfamily of proteins, now offers an intriguing new link between the coagulation and immune systems.

Hematopoietic placental protein 14. An immunosuppressive factor in cells of the megakaryocytic lineage.

Placental protein 14 (PP14), an immunosuppressive molecule previously known to be expressed in the female and male reproductive tracts only, was shown to be expressed by hematopoietic cells of the megakaryocytic lineage. Northern blot analysis confirmed the induction specificity of PP14 mRNA in phorbol ester-treated K562 cells. Potent immunosuppressive activity in conditioned medium from phorbol ester-treated K562 cells was attributed to hematopoietic PP14 by anti-PP14 antibody blocking. Immunoprecipitation with anti-PP14 antibodies from conditioned medium revealed two distinct PP14 protein isoforms, designated PP14.1 and PP14.2. Polymerase chain reaction cloning and analysis demonstrated the presence of distinct mRNA counterparts to PP14.1 and PP14.2 that had not been resolved by Northern blot analyses. Hematopoietic PP14.1 mRNA corresponds in size to endometrial PP14 mRNA, whereas the smaller hematopoietic PP14.2 mRNA displays an internal in-frame 66-nucleotide deletion that can be explained by alternative splicing and predicts a 22-amino-acid deletion in the encoded gene product. Both PP14 mRNA isoforms were additionally detected by reverse transcriptase polymerase chain reaction analyses in two human megakaryocytic cell lines and in normal human megakaryocytes and platelets. PP14 mRNA was not detected by reverse transcriptase polymerase chain reaction in a panel of nonhematopoietic, nonendometrial tissues examined. The finding of hematopoietic PP14 within the megakaryocytic lineage provides an additional regulatory link between the coagulation and immune systems in normal and pathological settings.

[Relation between dampness-heat syndrome of glomerulonephritis and sialic acid and N-acetyl-beta-D-glucosaminidase (NAG)].

Plasmic and urinary sialic acid and urinary N-acetyl-beta-D-glucosaminidase (NAG) of 87 glomerulonephritic patients with and without Dampness-Heat Syndrome were measured, and the influence of clearing up Dampness-Heat therapy on above-mentioned parameters was investigated. The results showed that Psa, Usa and UNAG of Dampness-Heat Syndrome were significantly higher than those of non-Dampness-Heat Syndrome (P < 0.05-0.01). The further analysis indicated that the patients with acute onset of chronic nephritis manifested as Dampness-Heat, showed marked positive correlation between Usa and UNAG as well as between UNAG and proteinuria respectively (r = 0.75 and 0.722, P < 0.001). With the treatment of Abelmoschus manihot which could remove the Dampness-Heat, the amount of proteinuria, Usa and UNAG were all significantly decreased (P < 0.05-0.001). It suggested that Usa and UNAG might be as diagnostic and curative parameters of Dampness-Heat of glomerulonephritis.

[Clinical and experimental studies on sanpin therapy for chronic cervical diseases].

Chronic cervical diseases belong to the category of precancerous diseases whose treatment is important in preventing cervical cancer. 135 cases were treated with Sanpin preparations therapy after exclusion of heart, liver, kidney and cancerous diseases. After the treatment of 2-3 months, 133 cases were cured. Two cases have not finished their treatment courses and so have been excluded from the study. Among them, 110 have been followed up for 1 to 11 years. All of the patients with pretreatmental hypertrophic cervices had normal sizes after the treatment. The cure rate of cervical erosion was 83.81% and the cure rate of cervical neoplasms was 91.84%. The basic studies of toxicology, pharmacology, pharmacochemistry and genetic toxicology of the Sanpin pills and rods have been done. Results showed that this therapy was safe so long as its indications and contraindications were handled correctly and the drug was given routinely. This therapy is simple, economical, safe and effective. After short training, it can be applied in county and township hospitals.