Bacteriocins have antimicrobial activities against food-spoiling bacteria and food-borne pathogens. Paracin 1.7, a bacteriocin synthesized by Lactobacillus paracasei HD1-7 isolated from Chinese sauerkraut juice, was studied. Following partial purification with ammonium sulfate precipitation, CM Sepharose Fast Flow, and Sephadex G-10 chromatography, the molecular weight of Paracin 1.7 was about 10 kDa based on Tricine-SDS-PAGE results. A 2.87 fold purified bacteriocin was produced, reaching a final yield of 39.93% and the specific activity of 1.56 × 10(3) AU/mg. The N-terminal amino acid sequence of Paracin 1.7 was VSNTFFA, and the LC/LTQ results revealed that the N-terminal amino acid sequence was similar to that of ABC-type oligopeptide transport system protein and N-acetylmuramoyl-L-alanine amidase. Paracin 1.7 was sensitive to protease K, had antimicrobial activities at a broad pH range (3.0-8.0), and was heat resistant (121 °C for 20 min). Paracin 1.7 from Lactobacillus paracasei HD1-7 is a novel bacteriocin that has potential applications in food preservation.

Most cancer patients receive radiotherapy in the course of their disease and the occurrence of radioresistance is associated with poor prognosis. The molecular pathways that drive enhanced tumorigenic potential during the development of radioresistance are poorly understood. Here, we demonstrate that aryl hydrocarbon receptor (AhR) plays a vital role in the maintenance of cancer stem-like properties. AhR promotes the cancer stem-like phenotype and drives metastasis by directly targeting the promoters of 'stemness' genes, such as the ATP-binding cassette sub-family G member 2 (ABCG2) gene. Moreover, the radioresistant sublines display high levels of oncometabolites including α-ketoglutarate, and treatment of cancer cells with α-ketoglutarate enhances their stem-like properties in an AhR activation-dependent manner. IKKα directly activates stemness-related genes through an interaction with AhR as a bone fide chromatin modifier. Thus, AhR is functionally linked with cancer stem-like properties, and it drives tumorigenesis in the occurrence of radioresistance.

This study systemically evaluated the efficacy and safety of intermittent intravenous pulse therapy with different doses of cyclophosphamide (CTX) for the treatment of lupus nephritis (LN).

Tamoxifen is a frontline therapy for estrogen receptor (ER)-positive breast cancer in premenopausal women. However, many patients develop resistance to tamoxifen, and the mechanism underlying tamoxifen resistance is not well understood. Here we examined whether ER-c-Src-HER2 complex formation is involved in tamoxifen resistance.

EvaGreen (EG) is a newly developed DNA-binding dye that has recently been used in quantitative real-time PCR (qPCR), post-PCR DNA melt curve analysis and several other applications. However, very little is known about the physicochemical properties of the dye and their relevance to the applications, particularly to qPCR and post PCR DNA melt curve analysis. In this paper, we characterized EG along with a widely used qPCR dye, SYBR Green I (SG), for their DNA-binding properties and stability, and compared their performance in qPCR under a variety of conditions.

Intrauterine adhesion (IUA) is characterized by endometrial fibrosis. S100A8/A9 plays an important role in inflammation and fibroblast activation. However, the role of S100A8/A9 in IUA remains unclear. In this study, we collect normal and IUA endometrium to verify the expression of S100A8/A9. Human endometrial stromal cells (hEnSCs) are isolated to evaluate fibrosis progression after S100A8/A9 treatment. A porcine IUA model is established by electrocautery injury to confirm the therapeutic effect of menstrual blood-derived stromal cells (MenSCs) on IUA. Our study reveals increased S100A8/A9 expression in IUA endometrium. S100A8/A9 significantly enhances hEnSCs proliferation and upregulates fibrosis-related and inflammation-associated markers. Furthermore, S100A8/A9 induces hEnSCs fibrosis through the RAGE-JAK2-STAT3 pathway. Transplantation of MenSCs in a porcine IUA model notably enhances angiogenesis, mitigates endometrial fibrosis and downregulates S100A8/A9 expression. In summary, S100A8/A9 induces hEnSCs fibrosis via the RAGE-JAK2-STAT3 pathway, and MenSCs exhibit marked effects on endometrial restoration in the porcine IUA model.

Induction of cell apoptosis and regulation of cell cycle are very attractive for treatments of tumors including ovarian carcinoma. Flavopiridol is a potent small molecular cyclin-dependent kinase(cdk) inhibitor, but its antitumor efficacy is not satisfied yet. Caspase-3 play a major role in the transduction of apoptotic signals and the execution of apoptosis in mammalian cells. We have successfully constructed the recombinant adenovirues AdHTVP2G5-rev-casp3 containing autocatalytic caspase-3 (rev-caspase-3) driven by amplified hTERT promoter system (TSTA-hTERTp). In this study, we applied it with flavopiridol to investigate their antitumor effect on ovarian cancer in vitro and in vivo.

Emerging knowledge has highlighted the role of periostin (POSTN) in osteoarthritis (OA) process; however, whether POSTN is suitable as a biomarker of OA remains unclear. This study aimed to investigate the potential value of POSTN as a biomarker of OA.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, which is very difficult to treat and commonly develops resistance to chemotherapy. The following study investigated whether the inhibition of Flap Endonuclease 1 (FEN1) expression, the key enzyme in the base excision repair (BER) pathway, could improve the anti-tumor effect of arsenic trioxide (ATO), which is a reactive oxygen species (ROS) inducer. Our data showed that ATO could increase the expression of FEN1, and the knockdown of FEN1 could significantly enhance the sensitivity of TNBC cells to ATO both in vitro and in vivo. Further mechanism studies revealed that silencing FEN1 in combination with low doses of ATO might increase intracellular ROS and reduce glutathione (GSH) levels, by reducing the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2); elevating ROS leaded to apoptosis and p38 and JNK pathway activating. In conclusion, our study suggested the combination of FEN1 knockdown and ATO could induce TNBC cell death by promoting ROS production. FEN1 knockdown can effectively decrease the application concentrations of ATO, thus providing a possibility for the treatment of TNBC with ATO.

Paclitaxel is one of the most effective chemotherapy drugs for breast cancer worldwide but 20‑30% patients show primary resistance to the drug. Screening and identification of markers that facilitate effective and rapid prediction of sensitivity to paclitaxel is therefore an urgent medical requirement. In the present study, G protein signaling modulator 2 (GPSM2) mRNA levels were significantly associated with taxane sensitivity in experiments based on the Gene Expression Omnibus (GEO) online database. Immunohistochemical analysis consistently revealed a significant association of GPSM2 protein levels with paclitaxel sensitivity in breast cancer patients. Knockdown of GPSM2 reduced the sensitivity of breast cancer cells to paclitaxel via regulation of the cell cycle. Animal experiments further corroborated our in vitro findings. These results suggest that GPSM2 plays an important role in breast cancer resistance, supporting its utility as a potential target for improving drug susceptibility in patients as well as a marker of paclitaxel sensitivity.

Nowadays, the vaccination with COVID-19 vaccines is being promoted worldwide, professionals and common people are very concerned about the efficacy and safety of COVID-19 vaccines. No published systematic review and meta-analysis has assessed the efficacy and safety of the COVID-19 vaccines based on data from phase III clinical trials. Therefore, this study has estimated the efficacy and safety of COVID-19 vaccines and the differences between vaccine types. PubMed, Embase, the Cochrane Library, CNKI, Wanfang, medRxiv databases and two websites were used to retrieve the studies. Random-effects models were used to estimate the pooled efficacy and safety with risk ratio (RR). A total of eight studies, seven COVID-19 vaccines and 158,204 subjects were included in the meta-analysis. All the vaccines had a good preventive effect on COVID-19 (RR = 0.17, 95% CI: 0.09-0.32), and the mRNA vaccine (RR = 0.05, 95% CI: 0.03-0.09) was the most effective against COVID-19, while the inactivated vaccine (RR = 0.32, 95% CI: 0.19-0.54) was the least. In terms of safety, the risk of overall adverse events showed an increase in the vaccine group after the first (RR = 1.46, 95% CI: 1.03-2.05) or second (RR = 1.52, 95% CI: 1.04-2.20) injection. However, compared with the first injection, the risk of local (RR = 2.64, 95% CI: 1.02-6.83 vs. RR = 2.25, 95% CI: 0.52-9.75) and systemic (RR = 1.33, 95% CI: 1.21-1.46 vs. RR = 1.59, 95% CI: 0.84-3.01) adverse events decreased after the second injection. As for the mRNA vaccine, the risk of overall adverse events increased significantly, compared with the placebo, no matter whether it was the first (RR = 1.83, 95% CI = 1.80-1.86) or the second (RR = 2.16, 95% CI = 2.11-2.20) injection. All the COVID-19 vaccines that have published the data of phase III clinical trials have excellent efficacy, and the risk of adverse events is acceptable. The mRNA vaccines were the most effective against COVID-19, meanwhile the risk and grade of adverse events was minimal, compared to that of severe symptoms induced by COVID-19.

Considering the essential roles that genetic factors play in azoospermia and oligospermia, this study aims to identify abnormal chromosomes using karyotyping and CNVs and elucidate the associated genes in patients.

The purpose of this study was to explore the relationship between SF3B1 mutations and the prognoses of patients with breast cancer. Clinical and SF3B1 mutation data from The Cancer Genome Atlas were analyzed. SF3B1 mutations were evaluated as prognostic factors in all breast cancer patients and specific subgroups through Cox regression and Kaplan-Meier analyses. We also investigated the relationship between traditional parameters and SF3B1 mutations. Receiver operating characteristics curves were used to analyze common risk factors for their sensitivity and specificity in predicting SF3B1 mutations. SF3B1 mutations were a poor prognostic factor in luminal B and progesterone receptor (PR)-negative breast cancer (P < 0.01). Age at diagnosis and estrogen receptor (ER) status were associated with SF3B1 mutations in all breast cancers (P < 0.01) and in luminal B and PR-negative subgroups (P < 0.01). The age at diagnosis and ER status combined had a higher sensitivity and specificity for predicting SF3B1 mutations than each factor alone. SF3B1 mutations are a poor prognostic factor in luminal B and PR-negative breast cancer patients. These mutations are significantly associated with age at diagnosis and ER status. SF3B1 mutations may therefore be a novel therapeutic target for breast cancer patients.

A new delivery method via polymeric implants was used for continuous exposure to PCBs. Female Sprague-Dawley rats received subcutaneous polymeric implants containing PCB126 (0.15% load), PCB153 (5% load), or both, for up to 45 days and release kinetics and tissue distribution were measured. PCB153 tissue levels on day 15 were readily detected in lung, liver, mammary and serum, with highest levels in the mammary tissue. PCB126 was detected only in liver and mammary tissues. However, a completely different pharmacokinetics was observed on co-exposure of PCB153 and PCB126, with a 1.8-fold higher levels of PCB153 in the liver whereas a 1.7-fold lower levels in the mammary tissue. PCB126 and PCB153 caused an increase in expression of key PCB-inducible enzymes, CYP 1A1/2 and 2B1/2, respectively. Serum and liver activities of the antioxidant enzymes, PON1 and PON3, and AhR transcription were also significantly increased by PCB126. 32 P-Postlabeling for polar and lipophilic DNA-adducts showed significant quantitative differences: PCB126 increased 8-oxodG, an oxidative DNA lesion, in liver and lung tissues. Adduct levels in the liver remained upregulated up to 45 days, while some lung DNA adducts declined. This is the first demonstration that continuous low-dose exposure to PCBs via implants can produce sustained tissue levels leading to the accumulation of DNA-adducts in target tissue and induction of indicator enzymes. Collectively, these data demonstrate that this exposure model is a promising tool for long-term exposure studies.

Microvesicles (MVs) are carriers of molecular and oncogenic signatures present in subsets of tumor cells and tumor-associated stroma, and a focus of cancer research. Although methods to detect MVs are mature, we were concerned that the buffer used could lead to false results when quantitating MVs by flow cytometry. In this work,we detected MVs by flow cytometry withthree different solutions: water, saline, and phosphate-buffered saline (PBS). The results demonstrated that PBS, when reacted with annexin V binding buffer, produced nano-sized vesicles even when there were no MVs in the sample. No similar events occurred in the saline and water groups (P < 0.01). Annexin V positive rate increased significantly when PBS was used as the buffer, compared to saline and water. These false negative results were also observed when we quantified some markers of MVs such as CD3 and CD19. A probable explanation for these findings is the production of insoluble Ca(H2PO4)2 or Ca3PO4 from calcium in the binding buffer and phosphate in PBS. Thus, considering the osmotic pressure of water, we suggest that saline is a more suitable buffer when counting MVs by flow cytometry.

Embryonic chromosomal abnormality is one of the significant causative factors of early pregnancy loss. Our goal was to evaluate the clinical utility of next-generation sequencing (NGS) technology in identifying chromosomal anomalies associated with first-trimester pregnancy loss. In addition, we attempted to provide fertility guidance to couples anticipating a successful pregnancy. A total of 1,010 miscarriage specimens were collected between March 2016 and January 2019 from women who suffered first-trimester pregnancy loss. Total DNA was isolated from products of conception, and NGS analysis was carried out. We detected a total of 634 cases of chromosomal variants. Among the 634 cases, 462 (72.9%) displayed numerical variants including 383 (60.4%) aneuploidies, 44 (6.9%) polyploidies, and 34 (5.5%) mosaicisms. The other 172 (27.1%) cases showed structural variants including 19 (3.0%) benign copy number variations (CNVs), 52 (8.2%) pathogenic CNVs, and 101 (16%) variants of unknown significance (VOUS) CNVs. When maternal age was ≥ 35 years, the sporadic abortion (SA) group showed an increased frequency of chromosomal variants in comparison with the recurrent miscarriage (RM) group (90/121 vs. 64/104). It was evident that the groups with advanced maternal age had a sharply increased frequency of aneuploidy, whatever the frequency of pregnancy loss (71/121 vs. 155/432, 49/104 vs. 108/349). Our data suggest that NGS could be used for the successful detection of genetic anomalies in pregnancy loss. We recommend that fetal chromosome analysis be offered routinely for all pregnancy losses, regardless of their frequency.

Gastric cancer is one of the top five malignant tumors worldwide. At present, the molecular mechanisms of gastric cancer progression are still not completely clear. Cytoplasmic dynein regulates intracellular transport and mitotic spindle localization, and its abnormal function is crucial for tumorigenesis, promotes tumor cell cycle progression, and tumor migration. DYNC1I1 is an important binding subunit of cytoplasmic dynein. However, studies on DYNC1I1 in tumors are currently limited. In the current study, we found that high DYNC1I1 expression in gastric cancer is associated with poor prognosis and is an independent prognostic factor. DYNC1I1 promoted the proliferation and migration of gastric cancer cells both in vitro and in vivo. DYNC1I1 also upregulated IL-6 expression by increasing NF-κB nuclear translocation. Collectively, these data revealed an important role for the DYNC1I1-driven IL-6/STAT pathway in gastric cancer proliferation and migration, suggesting that DYNC1I1 may be a potential therapeutic target for gastric cancer.

Background: Emerging knowledge has highlighted the role of matrix metalloproteinase (MMP)-13 in osteoarthritis (OA); however, the suitability of MMP-13 as a biomarker for OA remains unclear. Therefore, this study aimed to assess the potential value of MMP-13 as a biomarker for OA. Methods: The study enrolled 51 patients, of which 33 had advanced varus OA and 18 did not have OA. Immunohistochemistry and western blotting analyses were performed to measure MMP-13 activity in the cartilage and subchondral bone of patients with OA. Enzyme-linked immunosorbent assay was used to measure serum MMP-13 levels in patients with or without OA. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to assess the association between serum MMP-13 levels and clinical symptoms. Furthermore, the association between serum MMP-13 levels and radiological severity of OA was evaluated using the Kellgren-Lawrence (KL) grading system. Finally, we built the proportional odds logistic regression models to evaluate serum MMP-13 levels as a potential predictor for OA. Results: MMP-13 levels were significantly higher in the severe-worn cartilage of the medial tibial plateau than in the relatively intact portion of the lateral cartilage (p < 0.05). This was contrary to the findings for MMP-13 differential expression in the subchondral bone in knee OA (p < 0.05). Patients with OA had significantly higher serum MMP-13 levels compared with patients without OA. Additionally, remarkable associations among serum MMP-13 levels, WOMAC scores, and KL grading scores were found in the end-stage OA. Furthermore, the subsequent analysis suggested that serum MMP-13 level was a significant predictor for OA. Conclusion: MMP-13 is valuable for diagnosing, measuring disease severity, and predicting OA in the advanced period of the disease, suggesting that it has potential possibility as a biomarker for OA. However, the underlying mechanisms and clinical application of MMP-13 as a biomarker for OA require to be further investigated.

Vitamin D deficiency is a widespread issue globally, resulting in increased use of vitamin D supplements. However, it is unclear whether intermittent (weekly or monthly) vitamin D supplementation is as effective as daily supplementation in improving circulating 25-hydroxyvitamin D [25(OH)D] levels.