Knockdown of BMI1 Enhances The Sensitivity of Cervical and Endometrial Cancer Cells to Paclitaxel / 生物化学与生物物理进展

ObjectiveTo study the effects of BMI1 on the proliferation and drug resistance of cervical cancer (CC) and endometrial cancer (EC) cells. In addition, the mechanism of paclitaxel (PTX) resistance induced by BMI1 was explored. MethodsIn this study, we utilized the GTEx, Cbioportal, TCGA, and CPTAC databases to comprehensively analyze the mutation rate as well as mRNA and protein expression profiles of BMI1 in CC and EC. Subsequently, immunohistochemistry (IHC) analysis was employed to evaluate the protein expression levels of BMI1 in 40 pairs of CC and 40 pairs of EC tissue samples. Western blot was conducted to investigate alterations in downstream factor protein levels upon BMI1 knockdown in CC and EC cells. Furthermore, functional experiments were performed to elucidate the role of BMI1 in CC and EC cells. Finally, we assessed the synergistic anti-growth effect by combining BMI1 knockdown with paclitaxel treatment in vitro. ResultsThe Cbioportal database revealed that BMI1 amplification, misinterpretation, and splicing occurred in 1.5% of CC patients and 1.9% of EC patients. Mining the data from TCGA and CPTAC databases, high mRNA levels of BMI1 were associated with the pathological type of CC and lower overall survival, and high protein levels of BMI1 were related to EC’s pathological type and tumor grade. Furthermore, the BMI1 protein level is overexpressed in cancer tissues of CC and EC compared with normal tissues, as detected by IHC analysis. Besides, drug sensitivity experiments showed that overexpression of BMI1 resulted in decreased sensitivity of HeLa and HEC-1-A cells to a variety of anticancer drugs, including paclitaxel. In order to further analyze the relationship between BMI1 and paclitaxel resistance, Western blot was used to detect the changes in the protein levels of downstream factors of BMI1 in HeLa and HEC-1-A cells after BMI1 knockdown. The results showed that the level of anti-apoptotic factor Bcl-2 protein decreased, while that of pro-apoptotic factor BAX increased with BMI1 knockdown. Additionally, we showed that high expression of BMI1 promoted the proliferation and migration of CC and EC cells in vitro. Moreover, CC and EC cells with low BMI1 expression were more sensitive to the paclitaxel. ConclusionThe expression of BMI1 is significantly upregulated in tumor tissues from patients with cervical and endometrial cancer, and silencing BMI1 makes CC and EC cells more sensitive to paclitaxel via enhancing pro-apoptotic regulation.

Effect of breastfeeding on immune function in infants with human cytomegalovirus infection / 中国当代儿科杂志

OBJECTIVES@#To study the effect of breastfeeding on immune function in infants with human cytomegalovirus (HCMV) infection.@*METHODS@#A retrospective analysis was performed on the medical data of 135 infants with HCMV infection who were admitted to Children's Hospital Affiliated to Zhengzhou University from January 2021 to May 2022, and all these infants received breastfeeding. According to the results of breast milk HCMV-DNA testing, the infants were divided into two groups: breast milk HCMV positive (n=78) and breast milk HCMV negative (n=57). According to the median breast milk HCMV-DNA load, the infants in the breast milk HCMV positive group were further divided into two subgroups: high viral load and low viral load (n=39 each). Related indicators were compared between the breast milk positive and negative HCMV groups and between the breast milk high viral load and low viral load subgroups, including the percentages of peripheral blood lymphocyte subsets (CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, and CD19+ B cells), CD4+/CD8+ ratio, IgG, IgM, IgA, and urine HCMV-DNA load.@*RESULTS@#There were no significant differences in the percentages of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, and CD19+ B cells, CD4+/CD8+ ratio, IgG, IgM, IgA, and urine HCMV-DNA load between the breast milk HCMV positive and HCMV negative groups, as well as between the breast milk high viral load and low viral load subgroups (P>0.05).@*CONCLUSIONS@#Breastfeeding with HCMV does not affect the immune function of infants with HCMV infection.

The functional role of sulforaphane in intestinal inflammation: a review.

Intestinal inflammation represented by inflammatory bowel disease (IBD) has become a global epidemic disease and the number of patients with IBD continues to increase. This digestive tract disease not only affects the absorption of food components by destroying the intestinal epithelial structure, but also can induce diseases in remote organs via the gut-organ axis, seriously harming human health. Nowadays, increasing attention is being paid to the nutritional and medicinal value of food components with increasing awareness among the general public regarding health. As an important member of the isothiocyanates, sulforaphane (SFN) is abundant in cruciferous plants and is famous for its excellent anti-cancer effects. With the development of clinical research, more physiological activities of SFN, such as antidepressant, hypoglycemic and anti-inflammatory activities, have been discovered, supporting the fact that SFN and SFN-rich sources have great potential to be dietary supplements that are beneficial to health. This review summarizes the characteristics of intestinal inflammation, the anti-inflammatory mechanism of SFN and its various protective effects on intestinal inflammation, and the possible future applications of SFN for promoting intestinal health have also been discussed.

Two new species of a new genus, Pseudorogneda, of Polycystididae discovered in Southern China.

Two new species of the new genus Pseudorogneda of Polycystididae were discovered in a brackish environment from Southern China. Pseudorogneda sinensis n. gen. n. sp., is distinguished by a semicircular double-walled prostate stylet type II that tapers in diameter from proximal to distal with a proximal-to-distal fold, and an inner wall with a funnel-shaped base originating at the midpoint of the outer wall; its flattened tubular prostate stylet type IV exhibits a horn-like base and a proximal-to-distal folded structure on its wall. For Pseudorogneda shenda n. gen. n. sp., its crescent-shaped prostate stylet type II is double-walled and the inner wall has a funnel-shaped base that starts at the proximal 2/3 position of the outer stylet and is fused with the outer stylet to form a sharp distal end; its tubular and slightly-curved prostate stylet type IV exhibits a slit and a distal fold. Phylogenetic analysis of 18S rDNA and 28S rDNA sequences shows that the two novel species are clustered to form an independent clade from other genera, which is consistent with morphological comparison in the establishment of two new species in a new genus.

Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development

To discover new drugs to combat coronavirus disease 2019 (COVID-19), an understanding of the molecular basis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated and was positively correlated with disease course and severity in COVID-19 patients. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cell lines and human ACE2 transgenic mice, while CTSL overexpression, in turn, enhanced pseudovirus infection. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity and prevented SARS-CoV-2 pseudovirus infection. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.

Gastrointestinal stromal tumors of the rectum: Clinical, pathologic, immunohistochemical characteristics and prognostic analysis.

OBJECTIVE: To describe the clinical, pathological and immunohistochemical characteristics of rectal gastrointestinal stromal tumors (GISTs) and to correlate them with clinical outcomes. MATERIAL AND METHODS: A retrospective review of 29 patients with surgically treated rectal GISTs during the period from 1997 to 2005 was undertaken. The NIH (National Institute of Health Consensus) criteria were applied. RESULTS: All the rectal GISTs in our series originated in the lower half of the rectum and patients underwent primary surgery for complete resections; High-risk, intermediate-risk, low-risk and very low-risk GISTs were found in 11, 6, 5 and 7 patients, respectively. Necrosis, adjacent (mucosal or serosa) invasion and marked pleomorphisms were found in 10, 7 and 20 patients, respectively. Positive expression of CD117, CD34, SMA and S-100 was found in 28, 28, 7 and 3 patients, respectively. Twelve patients had recurrence or metastasis within the median disease-free survival time of 41 months. Among the patients who underwent local resections, the recurrence rate for low-risk and very low-risk GISTs was only 1/10; for intermediate-risk and high-risk GISTs, the recurrence rate after local resections was 3/4, which was higher than the recurrence and metastasis rate of 8/13 after laparotomy. Of the 12 patients with adverse outcomes, 4 patients underwent secondary complete resections; however, all 4 patients had further recurrences. On univariate analysis, risk classification (p = 0.0002), necrosis (p = 0.0205), adjacent invasion (p = 0.0090) and marked pleomorphism (p = 0.0480) were significant predictors of disease-free survival. In the Cox regression model, only the risk classification (p = 0.012) was found to be an independent factor. CONCLUSION: We found that rectal GISTs arise predominantly in the lower half of the rectum and have high CD117 and CD34 expression. Local resection may be a good choice for very-low-risk and low-risk GISTs, but aggressive surgery may be more beneficial for high-risk and intermediate-risk GISTs. For patients with disease recurrence, the results of secondary surgery were poor. Only the NIH risk classification proved to be an independent prognostic factor for rectal GISTs, whereas the proof for other factors was insufficient.

Effect of Local Intramuscular Repeated Injection with Botulinum Toxin-A for Treatment of Spastic Cerebral Palsy / 实用儿科临床杂志

Objective To observe the curative effect of botulinum toxin A(BTX-A)repeated intramuscular injection for treatment of serious spastic cerebral palsy.Methods Thirty cases with serious spastic cerebral palsy received local repeated intramuscular injection. The interval time was 3 months. The dose of BTX-A was 4 U/kg.The muscle tone was assessed with the modified ashworth scale and range of motion with physical rating scale(PRS).The indexes were evaluated before injection and 3 months after the second injection. Paired-samples t-test was used in the statistic analysis.Result The muscle tone and PRS had remarkable improvement after second therapy with BTX-A(P

Studies on the effect of dihydromyricetin on antilipid-peroxidation / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effects of Dihydromyricetin (DMY) on antilipid-peroxidation.</p><p><b>METHOD</b>The antilipid-peroxidation of DMY on heart, liver, brain tissue homogenate and mitochondria was measured by the determination of malondiadehyde (MDA) induced by Fe2+ -Vit C, Fe2+ -H2O2, Fe-Cys with TBA spectrometric method.</p><p><b>RESULT</b>DMY could inhibit the lipid peroxidation of homogenate and mitochondria. The inhibition exhibited concentration-dependent manner.</p><p><b>CONCLUSION</b>DMY has good antilipid-peroxidation effect, which is worth studing further.</p>