Effects of grape seed-derived proanthocyanidin B2 pretreatment on oxidative stress, endoplasmic reticulum stress and apoptosis of renal tubular epithelial cells in renal ischemia-reperfusion injury model of mice.

PURPOSE: To investigate the effect of grape seed-derived proanthocyanidin B2 (GSPB2) pretreatment on acute renal ischemia-reperfusion injury model of mice. METHODS: 50 mice were divided into 5 groups: Sham group: mice were treated with right nephrectomy. GSPB2 group: GSPB2 was injected intraperitoneally 45 min before right nephrectomy. IRI group: right kidney was resected and the left renal arteriovenous vessel was blocked for 45 min. GSPB2 + IRI group: GSPB2 was intraperitoneally injected 45 min before IRI established. GSPB2 + BRU + IRI group: GSPB2 and brusatol (BRU) were injected intraperitoneally 45 min before IRI established. Creatinine and urea nitrogen of mice were detected, and the kidney morphology and pathological changes of each group were detected by HE staining, PAS staining and transmission electron microscopy. Expressions of Nrf2, HO-1, GRP78, CHOP, and cleaved-caspase3 were detected by immunofluorescence staining and western blotting. RESULTS: Morphology and mitochondrial damages of kidney in GSPB2 + IRI group were significantly alleviated than those in IRI group. Expression levels of Nrf2 and HO-1 were significantly higher in GSPB2 + IRI group than those in IRI group. Expression levels of GRP78, CHOP and cleaved-caspase3 were significantly lower in GSPB2 + IRI group than those in IRI group. However, compared to GSPB2 + IRI group, protective effects of GSPB2 pretreatment were weakened in GSPB2 + BRU + IRI group. CONCLUSIONS: GSPB2 pretreatment could alleviate oxidative stress damage and reduce apoptosis of renal tubular epithelial cells, which might be related to activating the antioxidant system, up-regulating the expression of Nrf2 and HO-1, inhibiting the expressions of GRP78, CHOP and cleaved-caspase3. However, the protective effect could be reversed by brusatol.

Stilbenes with potent cytotoxicity from the seedcases of Paeonia suffruticosa Andrews.

Stilbenes (based on the 1,2-diphenylethylene skeleton) are a class of plant polyphenols with rich structural and bioactive diversity. Twenty-six stilbenes, including five undescribed compounds (7,8-dioxy-4,3',5'-trihydroxystilbene, trans-13'-methoxygnetin H, suffruticosol E, paestibenetrimerols A and B), were isolated from the seedcases of Paeonia suffruticosa Andrews. Their structures were elucidated by spectroscopic analyses and comparison with previously reported data. The absolute configurations of trans-13'-methoxygnetin H, suffruticosol E, paestibenetrimerols A and B were assigned from their respective electronic circular dichroism (ECD) spectra. Additionally, the structures of known compounds suffruticosols A, B and rockiol B were revised and the absolute configurations of them, and along with (+)-davidiol A, were also further determined by ECD. The isolated compounds, trans-gnetin H, cis-gnetin H and suffruticosol E, were found to have potent cytotoxicity against the DU-145 and MDA-MB-231 cell lines with IC50 values of 4.89-8.61 µM. The preliminary antitumor structure-activity relationship of these stilbenes is discussed as well.

Antagonism of Lentinan on sodium arsenite induced hepatotoxicity in mice / 公共卫生与预防医学

Objective To explore the intervention effects of lentinan on sodium arsenite (SA) induced hepatotoxicity in mice. Methods Healthy male C57BL/6 mice were used as experimental subjects and divided into 4 groups, namely control group, SA treatment group, lentinan intervention + SA exposure group, and lentinan intervention control group. The mice were given oral SA (10.0 mg/kg.bw, once every other day) for 14 days, and then the liver tissues and serum samples were collected. Hematoxylin-eosin (HE) was used to evaluate the characteristics of hepatic pathological damage. Enzyme-linked immunosorbent assay (ELISA), Flow Cytometry (FC) and Western-blotting (WB) were used to detect the levels of hepatic function, oxidative stress, CD4+ type 17 helper T cells (Th17), and inflammatory cytokines. Results Compared with the control group, the arsenic exposure group showed obvious hepatic pathological injury and increased levels of serum ALT (8.78±0.76 vs 5.47±0.49) and AST (12.42±1.87 vs 7.14±0.57), FC experiments showed that the Th17 content in liver tissues increased (67.70±4.94 vs 7.36±1.50), and ELISA showed that the antioxidant GSH content decreased (593.40±23.25 vs 730.94±30.81), and the levels of MDA (74.56±7.63 vs 49.90±6.42) and proinflammatory cytokines IL-17A (162.48±10.75 vs 118.53±7.92) and IL-1β (512.50±24.78 vs 462.48±22.15) increased in hepatic tissues (P < 0.05). Compared with the arsenic exposure group, the lentinan showed a significant antagonistic effect after intervention (P < 0.05). Compared to SA exposure group, WB analysis showed that compared with the arsenic exposure group, the expression levels of IL-17A (0.47±0.08 vs 0.89±0.11) and NLRP3 inflammasome (0.80±0.09 vs 1.09±0.16) in the liver tissues of the lentinan intervention group were significantly decreased (P < 0.05). Conclusion Lentinan alleviates SA-induced hepatic injury in mice, which may be mediated through the inhibition of Th17-IL-17A inflammatory signaling.

Danggui Sini decoction treatment of refractory allergic cutaneous vasculitis: A case report.

BACKGROUND: Allergic cutaneous vasculitis (ACV) is a difficult disease to treat. At present, there is no effective treatment for this condition. Traditionally, immunosuppressants and hormones have been primarily used in its management, but the treatment effect is suboptimal, and it has several side effects. CASE SUMMARY: We present the case of a 19-year-old woman who presented at our hospital with a four-year history of symmetric skin lesions mainly affecting her lower extremities. She had previously undergone treatment with prednisolone acetate, cetirizine hydrochloride, and loratadine tablets but had not experienced any relief in her condition. Thereafter, she was treated with oral traditional Chinese medicine. Her skin damage gradually improved within two months of treatment initiation. After six months, the skin ulcers had completely subsided. No evidence of skin ulcer recurrence was observed during the subsequent follow-up. This report presents the first case of a female patient who received oral Danggui Sini decoction for the treatment of ACV. CONCLUSION: Danggui Sini decoction may be a promising oral treatment for ACV patients.

[Iodine Nutritional Status and Prevalence of Thyroid Disorders among Adults in Chengdu].

Objective: To investigate the prevalence of thyroid disorders, iodine nutritional status and relevant risk factors among adults in Chengdu city on the basis of two population-based surveys, one conducted between 2016 and 2017 and the other, between 2019 and 2020, and to provide references for making health-related administrative decisions. Methods: Two population-based sampling surveys were conducted. The first one was done between October 2016 and December 2017, using stratified cluster random sampling to select subjects from 2 urban and 2 rural communities in Chengdu. Then, between December 2019 and February 2020, sequential cluster sampling was used to select subjects from communities in the peripheral regions of Longquanyi District, Chengdu. Both surveys covered natural populations of people who were 18 or older and who met the inclusion criteria. In the first survey, questionnaires, physical examination, thyroid ultrasound, and examinations of serum thyroid biochemical markers and urine iodine were performed, while in the second survey, only questionnaire concerning thyroid disorders and physical examination were performed. Statistical analysis of the nutritional status of iodine, the prevalence of thyroid disorders, and potential risk factor was conducted. Results: A total of 1859 subjects were enrolled for the first survey and 16152 for the second. According to the results of the first survey, the median urine iodine concentration was 172.10 µg/L, and the group with adequate or more than adequate iodine accounted for more than 60% of the surveyed population. The prevalence of thyroid disorders was found to be 0.48% for overt hyperthyroidism, 0.43% for subclinical hyperthyroidism, 0.43% for Grave's disease, 1.34% for overt hypothyroidism, 16.62% for subclinical hypothyroidism, 16.73% for positive thyroid antibody, 12.96% for TPOAb positive, 10.06% for TGAb positive, 0.81% for goiter, 14.85% for single nodule, 14.42% for multi-nodules, and 29.26% for thyroid nodules. Excess iodine is a risk factor for subclinical hypothyroidism ( OR=1.50, 95% confidence interval [ CI]: 1.07-2.10, P<0.05), and iodine deficiency is a risk factor for multiple thyroid nodules ( OR=1.45, 95% CI: 1.02-2.05, P<0.05). The total prevalence of hyperthyroidism, hypothyroidism and Hashimoto's thyroiditis in the two surveys was 6.58% and 5.95%, respectively, showing no significant difference. The second survey lacked accurate data on thyroid nodules. Conclusion: The iodine nutritional status of adults in Chengdu in recent years was appropriate. The total prevalence of hyperthyroidism, hypothyroidism and Hashimoto's thyroiditis remained stable, while that of thyroid nodule increased in recent years. We should continue with the implementation of the universal salt iodization policy and reinforce efforts in monitoring. Furthermore, we should make an active effort to look into the etiology of thyroid nodules.

Safety Assessment of Canola Oil Extracted by Aid of Pulsed Electric Field: Genetic, Acute and Subacute Toxicity.

Pulsed electric field (PEF) is a nonthermal technology resulting in the rupture of cell membranes and increasing the electrical conductivity and the permeability of intracellular material. There was little work about the safety of food treated by PEF. The acute, subacute oral, and genetic toxicities were investigated to explore the safety of canola oil extracted by aid of PEF treatment (PTCO). The results showed that no negative consequences were caused by PEF. PTCO was regarded as practically non-toxic with a LD50 higher than 40 g/kg bw. No oil intake-related mortality, clinical, weight gain and organ coefficient abnormalities were observed. The histopathological symptoms indicated a mild load but not obvious toxicities on liver and kidney. The 28-day subacute toxicity test confirmed that less than 10 g/kg·d bw of oil intake did not exhibit any intake-related changes in physical, physiological, biochemical, hematological, and histopathological signs. The less than 4 of atherosclerosis index suggested that no risk of cardiovascular disease caused by PTCO intake. It was speculated that the PEF treatment would not cause any safety issues to food products.

Construction of Glycolytic Regulator Gene Signature to Predict the Prognosis and Tumor Immune Cell Infiltration Levels for Prostate Cancer.

Prostate cancer (PCa) is the commonly generated noncutaneous neoplasm among men worldwide. Glycolysis had been validated to promote cancer progression. However, the clinical significance of glycolytic regulators in PCa was not well understood. Here, we discovered that glycolytic regulators were dysregulated in PCa samples using GSE8511, GSE6919, and GEPIA. By detecting the expression of these regulators in PCa samples, we found that SLC2A1, SLC2A3, HK2, PFKFB2, TPI1, PKM2, and LDHA had higher expression in PCa compared with normal tissues. Moreover, both higher expression of TPI1, ALDOA, ENO1, LDHA, and PKM and lower expression of LDHB and HK2 were significantly related to shorter progression-free survival time in PCa. Of note, an 8 gene-based risk score was further constructed and confirmed to have a good performance in predicting progression-free survival (PFS) time in PCa. The signature risk score significantly correlated with NK cell, neutrophil cell, macrophage M2 cell, and myeloid dendritic cell infiltration levels in PCa. After bioinformatics analysis, our data suggested glycolytic regulators participated in the regulation of multiple nonmetabolic biological processes, such as RNA transport, biosynthesis of antibiotics, and cell cycle. We recapitulate that the glycolytic regulator signature was a prospective indicator for prognosis and immune cell infiltration levels in PCa.

High Expression of SLC16A1 as a Biomarker to Predict Poor Prognosis of Urological Cancers.

OBJECTIVE: Tumor metabolism has always been the focus of cancer research. SLC16A1, as a key factor in catalysis of monocarboxylate transport across the plasma membrane, has been found to be associated with the occurrence and metastasis of a variety of cancers, but its prognostic significance and mechanism in different tumors are still unclear. METHODS: Based on the gene expression matrix and clinical information of human cancer tissues acquired from TCGA and GTEX databases, the differential expression of SLC16A1 in different tumors and normal tissues was analyzed. To confirm the association between its expression, the mutation of MMRS gene, and the expression level of DNMTs. Univariate Cox regression was applied to analyze the association between SLC16A1 expression and patient prognosis. The effect of SLC16A1 expression on patient survival was examined by Kaplan Meier analysis. GSEA was used to identify related signaling pathways. RESULTS: The expression of SLC16A1 was differentially expressed in most tumors, especially in the urinary tract where it is commonly highly expressed, and differential expression of SLC16A1 in different clinical stages. SLC16A1 expression was significantly positively correlated with MMRS gene mutation and DNMTS expression. Moreover, high SLC16A1 expression was associated with poorer overall survival (OS) and progression-free survival (PFS) in urological cancers. In particular, the results of the enrichment analysis showed that SLC16A1 was associated with processes such as cell adhesion and many signaling pathways affecting cell cycle were significantly enriched in the group with high-expressed SLC16A1. CONCLUSION: SLC16A1 expression was upregulated in urological cancer. SLC16A1 may promote tumor development by regulating the epigenetic process of urological cancer and demonstrated a great potential as a prognostic biomarker of urological cancer patients.

Gene Expression Analysis Reveals Key Genes and Signalings Associated with the Prognosis of Prostate Cancer.

It is urgent to identify novel biomarkers for prostate cancer (PCa) prognosis and to understand the mechanisms regulating the tumorigenesis for PCa treatment. In this study, GSE17951 and TCGA were used to identify the differentially expressed genes (DEGs). Our study demonstrated that 1533 genes with increased expression and 2301 genes with decreased expression in PCa. Bioinformatics analysis data indicated that these up-regulated genes had an association with the modulation of mitotic nuclear division, sister chromatid cohesion, cell division, and cell cycle. Additionally, our results revealed downregulated genes took part in modulating extracellular matrix organization, angiogenesis, signal transduction, and Ras signaling pathway. Hub upregulated and downregulated PPI networks were identified by protein-protein interaction (PPI) network analysis and MCODE analysis. Of note, 12 cell cycle regulators, comprising CCNB1, CCNB2, PLK1, TTK, AURKA, CDC20, BUB1, PTTG1, CDC45, CDC25C, CCNA2, and BUB1B, were demonstrated to function crucially in PCa development. By detecting their expression in PCa cell lines, we confirmed that these cell cycle regulator expressions were heightened in PCa cells. GEPIA databases analysis showed that higher expression of these cell cycle regulators was correlated to shorter disease-free survival (DFS) time in PCa samples. Our findings collectively suggested targeting cell cycle pathways may offer novel prognosis and treatment biomarkers for PCa.

Marinomonas vulgaris sp. nov., a marine bacterium isolated from seawater in a coastal intertidal zone of Zhoushan island.

A Marinomonas-like, Gram-stain-negative, strictly aerobic and rod to ovoid-shaped bacterium, designated as strain A79T, was isolated from the seawater mixtures of oyster shells and brown algae in a coastal intertidal zone of Zhoushan, China. The strain was positive for oxidase and catalase. Colonies grown on marine agar for 48 h were round, milky white, smooth and moist with the diameter of 2-3 mm. Growth was observed at 15-30 °C (optimum, 25℃), pH 5.5-9.5 (optimum, pH 8.5) and with 0.5-8% (w/v) NaCl (optimum, 2-2.5%). The G + C content based on the genome sequence was 46.0%. The only respiratory quinone was Q-8. The main polar lipids contained phosphatidylglycerol, phosphatidylethanolamine, unidentified glycolipids, unidentified phospholipid and three unidentified lipids. The major fatty acids (> 10%) were C16:0, Summed feature 3 (comprising C16:1 ω6c and/or C16:1 ω7c) and summed feature 8 (comprising C18:1 ω6c and/or C18:1 ω7c). The 16S rRNA gene sequence similarity between strain A79T and Marinomonas pollencensis IVIA-Po-185T was 97.4%, the similarities with other type strains of the genus Marinomonas were 93.8-96.7%. Based on the results, Marinomonas vulgaris sp. nov. was proposed as a novel species. The type strain is A79T (= MCCC 1K05799T = KCTC 82519T = JCM 34473T).

Screening of non-alcoholic steatohepatitis (NASH)-related datasets and identification of NASH-related genes.

Non-alcoholic steatohepatitis (NASH) is a common liver disease in the western world. The mechanisms behind NASH formation are poorly understood, but there may be multiple targets considering the disease's multifactorial nature. To explore the genes related to the pathogenesis of NASH, we downloaded clinical data and gene expression of NASH patients from the Gene Expression Omnibus database (GEO). We identified 281 genes with a common expression in two NASH-related datasets (GSE89632 and GSE83452), suggesting that they may be related to NASH. Further study showed that Angptl4, Foxo1, and Ttc39B might be essential for NASH progression, and these have been poorly studied. Therefore, we explored their roles in NASH. Our data show that these genes participate in the development of NASH through lipid metabolism. This suggests that the three genes can be used as therapeutic targets in NASH.

Complete genome sequence of marine Roseobacter lineage member Monaibacterium sp. ALG8 with six plasmids isolated from seawater around brown algae.

Monaibacterium sp. ALG8 (=MCCC 1 K04733) was isolated from seawater around brown algae. The genome of Monaibacterium sp. ALG8 was sequenced, one circular 3,036,380 bp chromosome and six circular plasmids ranging from 12,229 to 151,263 bp were found after assembly. The results of genomic annotation showed that Monaibacterium sp. ALG8 lacks the ability to degrade alginate, indicating its ecological role may not be directly related to the degradation of brown algae. The comparison of genomic features in the plasmids showed that almost all of these plasmids, except pALG4, were horizontally recruited from donors, not ancestors. Based on predicted functions, the existence of plasmids may provide strain ALG8 with advantages including nitrate reduction, tolerance of osmotic stress via glycine betaine, resistance to heavy metal stress such as mercury and cobalt, degradation of benzoate metabolites such as p-cumate, transformation of the swim-or-stick lifestyle and improvement of the immune system with two CRISPR-Cas systems. This study provides evidence for the carbon metabolic patterns of Monaibacterium sp. ALG8 and predicts the functions and donors of six plasmids in this strain, broadening our understanding of the ecological roles of bacteria in the environment around brown algae and the functions and evolutionary patterns of plasmids in marine Roseobacter lineage members.

In silico screening identifies a novel small molecule inhibitor that counteracts PARP inhibitor resistance in ovarian cancer.

Poly ADP-ribose polymerase (PARP) inhibitors are promising targeted therapy for epithelial ovarian cancer (EOC) with BRCA mutations or defective homologous recombination (HR) repair. However, reversion of BRCA mutation and restoration of HR repair in EOC lead to PARP inhibitor resistance and reduced clinical efficacy of PARP inhibitors. We have previously shown that triapine, a small molecule inhibitor of ribonucleotide reductase (RNR), impaired HR repair and sensitized HR repair-proficient EOC to PARP inhibitors. In this study, we performed in silico screening of small molecule libraries to identify novel compounds that bind to the triapine-binding pocket on the R2 subunit of RNR and inhibit RNR in EOC cells. Following experimental validation of selected top-ranking in silico hits for inhibition of dNTP and DNA synthesis, we identified, DB4, a putative RNR pocket-binding inhibitor markedly abrogated HR repair and sensitized BRCA-wild-type EOC cells to the PARP inhibitor olaparib. Furthermore, we demonstrated that the combination of DB4 and olaparib deterred the progression of BRCA-wild type EOC xenografts and significantly prolonged the survival time of tumor-bearing mice. Herein we report the discovery of a putative small molecule inhibitor of RNR and HR repair for combination with PARP inhibitors to treat PARP inhibitor-resistant and HR repair-proficient EOC.

Management of Sonographically Suspicious Thyroid Nodules 1 cm or Smaller and Candidacy for Active Surveillance: Experience of a Tertiary Center in China.

OBJECTIVE: Our objective was to investigate the management of patients with asymptomatic suspicious thyroid nodules ≤1 cm. METHODS: We retrospectively reviewed medical records of patients with sonographically suspicious thyroid nodules ≤1 cm and without distant metastases, suspicious lymph node metastasis (LNM), or extrathyroidal extension (ETE). RESULTS: Of the 386 enrolled patients, 174 (45.1%) had immediate surgery (IS), while 212 (54.9%) underwent active surveillance (AS). In the IS group, 166 (95.4%) patients were confirmed as having papillary thyroid microcarcinoma. LNM and ETE were observed in 24.7% and 2.4% cases, respectively. In the AS group, nodule size increased by ≥3 mm in 11 (5.2%) patients and 39 (18.4%) had a >50% increase in nodule volume after a median follow-up of 12 months. Nodules with smaller volume at diagnosis were more likely to increase in volume later. Newly suspicious LNM was detected in 23 (10.8%) patients. Delayed surgery (DS) was performed in 101 patients, with 27 showing disease progression. ETE and LNM were detected in 3% and 36%, respectively, of patients with papillary thyroid microcarcinoma. Compared with IS, tumors in the DS group more frequently showed lateral LNM and capsular invasion (P < .05). No patient had recurrence or died of thyroid cancer during postoperative follow-up (median 26 [4-60] months). CONCLUSIONS: IS or DS of patients with asymptomatic suspicious thyroid nodules ≤1 cm was relatively high in China. The inertia of low-risk nodules and the effectiveness of DS for those that progressed make AS a feasible strategy.

Blended Teaching Practice of Molecular Biology Driven by Discipline Frontiers / 中国生物化学与分子生物学报

Molecular Biology is the core course of biology major, whose fundamentals are classical and which develops rapidly as well. The introduction of the discipline frontiers is an ideal way to enhance the vitality of the classroom. Based on MOOC resources, the course group combined online independent study and offline face to face class to implement blended learning. Driven by the discipline frontiers, diversified teaching methods were introduced and classroom ecology was reconstructed. Multiple teaching sessions, including students’ independent study, questioning and presentation, class leading role of the teachers, questions and answers and knowledge expansion have been rolled out and unified so as to cultivate the science and humanity spirit of the students and enhance the vitality of the classroom. This blended teaching model effectively exercises students’ innovative thinking, improves students’ participation, and plays a positive role in enriching learning experience, stimulating professional dream and promoting students’ enlightenment.

Progress in the research of application of hot springs in health care and adjuvant treatment of diseases / 上海预防医学

Hot spring is a kind of precious natural water resource formed under specific geological conditions and obtained by natural gushing or artificial drilling, and is rich in minerals and trace elements peculiar to deep strata. Hot spring bathing is a physical therapy with a long history. An increasing number of studies have shown the positive effects of hot spring bathing in maintaining health and the auxiliary treatment and rehabilitation of chronic diseases. This paper reviews the distribution, classification and application history of hot springs, and further explores the research on the effect of hot springs on the improvement of sub-health status and the adjuvant treatment of chronic diseases such as skin diseases, cardiovascular diseases and joint diseases, so as to provide reference for further understanding of the physiotherapy value of hot spring bathing and boost its role in the development of big health industries.

Effects of grape seed proanthocyanidin B2 pretreatment on oxidative stress and renal tubular epithelial cell apoptosis after renal ischemia reperfusion in mice.

PURPOSE: To investigate the effects of grape seed proanthocyanidin B2 (GSPB2) preconditioning on oxidative stress and apoptosis of renal tubular epithelial cells in mice after renal ischemia-reperfusion (RIR). METHODS: Forty male ICR mice were randomly divided into 4 groups: Group A: mice were treated with right nephrectomy. Group B: right kidney was resected and the left renal vessel was clamped for 45 minutes. Group C: mice were intraperitoneally injected with GSPB2 before RIR established. Group D: mice were intraperitoneally injected with GSPB2 plus brusatol before RIR established. Creatinine and urea nitrogen of mice were determined. Pathological and morphological changes of kidney were checked. Expressions of Nrf-2, HO-1, cleaved-caspase3 were detected by Western-blot. RESULTS: Compared to Group B, morphology and pathological damages of renal tissue were less serious in Group C. Western-blot showed that expressions of Nrf-2 and HO-1 in Group C were obviously higher than those in Group B. The expression of cleaved-caspase3 in Group C was significantly lower than that in Group B. CONCLUSION: GSPB2 preconditioning could attenuate renal oxidative stress injury and renal tubular epithelial cell apoptosis by up-regulating expressions of Nrf-2 and HO-1 and down-regulating the expression of cleaved-caspase-3, but the protective effect could be reversed by brusatol.

[CCL2 promotes angiogenesis of primary rat cardiac microvascular endothelial cells].

The aim of the present study was to investigate the role of chemokine CCL2 in angiogenesis of primary adult rat cardiac microvascular endothelial cells (CMEC). The rat CMECs were isolated and identified through morphology examination and immunostaining with CD31 and factor VIII antibodies. The angiogenesis of CMEC on Matrigel was evaluated at different time points. The expression and secretion of CCL2 during the process of angiogenesis was detected by real-time RT-PCR and ELISA, respectively. The results showed that, the primary rat CMEC was isolated successfully, and the angiogenesis of CMEC was significantly induced after Matrigel treatment for 4 h. The expression of CCL2 and CCR2 were increased during angiogenesis, and the secretion of CCL2 was detected after 2 h of angiogenesis and reached the peak concentration of 1 588.1 pg/mL after 4 h. Either CCL2 blocking antibody or CCR2 antagonist significantly reduced the angiogenesis of CMEC. These results suggest that CCL2 is secreted during the process of angiogenesis of CMEC, and CCL2/CCR2 signaling pathway may play an important role in promoting angiogenesis.

Knockout of glutathione peroxidase 5 down-regulates the piRNAs in the caput epididymidis of aged mice.

The mammalian epididymis not only plays a fundamental role in the maturation of spermatozoa, but also provides protection against various stressors. The foremost among these is the threat posed by oxidative stress, which arises from an imbalance in reactive oxygen species and can elicit damage to cellular lipids, proteins, and nucleic acids. In mice, the risk of oxidative damage to spermatozoa is mitigated through the expression and secretion of glutathione peroxidase 5 (GPX5) as a major luminal scavenger in the proximal caput epididymidal segment. Accordingly, the loss of GPX5-mediated protection leads to impaired DNA integrity in the spermatozoa of aged Gpx5-/- mice. To explore the underlying mechanism, we have conducted transcriptomic analysis of caput epididymidal epithelial cells from aged (13 months old) Gpx5-/- mice. This analysis revealed the dysregulation of several thousand epididymal mRNA transcripts, including the downregulation of a subgroup of piRNA pathway genes, in aged Gpx5-/- mice. In agreement with these findings, we also observed the loss of piRNAs, which potentially bind to the P-element-induced wimpy testis (PIWI)-like proteins PIWIL1 and PIWIL2. The absence of these piRNAs was correlated with the elevated mRNA levels of their putative gene targets in the caput epididymidis of Gpx5-/- mice. Importantly, the oxidative stress response genes tend to have more targeting piRNAs, and many of them were among the top increased genes upon the loss of GPX5. Taken together, our findings suggest the existence of a previously uncharacterized somatic piRNA pathway in the mammalian epididymis and its possible involvement in the aging and oxidative stress-mediated responses.

Primary prostate cancer synchronous with renal cell carcinoma: clinical experience and literature review.

The objective of this study was to report the diagnosis and treatment results of primary prostate adenocarcinoma (PRAD) concurrent in a patient with renal cell carcinoma (RCC), and to review the relative literature. A 62-year-old man was admitted to our hospital with chief complaint of a painless, incidentally found renal mass for one year. RCC was initially found by computed tomography (CT) scan, but prostate cancer was incidentally found by abnormal prostate-specific antigen (PSA) level results. The post-nephrectomy pathology assay reported clear RCC with positive staining of vimentin, cluster of differentiation 10 (CD10), carbonic anhydrase IX (CA-IX), paired box 8 (Pax-8), epithelial membrane antigen (EMA), and Ki67 labeling index (Ki67 LI). Magnetic resonance imaging (MRI) revealed uneven signals in the right peripheral zone of the prostate. Both prostate biopsy and post-prostatectomy pathology examination revealed prostate acinar adenocarcinoma with positive staining of P504S and Ki67 LI. The patient has been in periodic follow-up and has remained in good general condition without any evidence of recurrence to date. To the best of our knowledge, the present report is the only case of systematically described pre- and post-therapy laboratory, pathology, and imaging examination results. Our report together with published studies suggest that increased awareness of synchronous PRAD risk will enable early detection and prompt therapies in patients with RCC.