Knowledge, attitudes, and practices (KAPs) regarding tick-borne rickettsial disease among medical staff in endemic areas of China.

Tick-borne rickettsial disease (TBRD) is a perilous acute infection that often eludes diagnosis in its early stages. The triad of knowledge, attitudes, and practices (KAPs) among medical professionals is key to reducing missed diagnosis rates. Therefore, a meticulous evaluation of KAPs is imperative. This study aimed to delve into the understanding of TBRD and explore the beliefs and practices related to personal prevention methods among individuals in Lu'an, a hotspot for TBRD. During the summer months of 2023, convenience sampling was employed by circulating a confidential questionnaire to 1,206 participants in the endemic regions of China. This questionnaire painted a comprehensive picture of the participants' sociodemographic profiles and their KAPs levels vis-à-vis TBRD. The findings revealed that participants scored a mere 55.78% in knowledge, while their attitudes and practices garnered impressive scores of 90.09% and 90.83%, respectively. Upon further analysis using multiple linear regression, several intriguing patterns emerged. Male participants, employed in the Infectious Disease Department, held vice-senior or higher titles, or had prior medical training demonstrated superior knowledge scores. On the other hand, medical personnel who were younger than 30, possessed graduate degrees or higher qualifications, and had training excelled in attitudes and practices. Notably, when employing the Boston Consulting Group (BCG) matrix, a significant distribution of medical personnel was observed across the four quadrants. Specifically, 37.43%, 13.19%, 19.61%, and 29.77% fell into the first, second, third, and fourth quadrants. This survey underscores the commendable attitudes and practices of medical staff towards TBRD in endemic regions of China. However, their knowledge level remains wanting and demands urgent improvement.

LUC7L3 is a downstream factor of SRSF1 and prevents genomic instability.

The RNA-binding protein LUC7L3 is the human homolog of yeast U1 small nuclear RNA (snRNA)-related splicing factor Luc7p. While the primary function of LUC7L3 as an RNA-binding protein is believed to be involved in RNA metabolism, particularly in the splicing process, its exact role and other functions are still not fully understood. In this study, we aimed to elucidate the role of LUC7L3 and its impact on cell proliferation. Our study revealed that LUC7L3 depletion impairs cell proliferation compared to the other Luc7p paralogs, resulting in cell apoptosis and senescence. We explored the underlying mechanisms and found that LUC7L3 depletion leads to R-loop accumulation, DNA replication stress, and genome instability. Furthermore, we discovered that LUC7L3 depletion caused abnormalities in spindle assembly, leading to the formation of multinuclear cells. This was attributed to the dysregulation of protein translation of spindle-associated proteins. Additionally, we investigated the interplay between LUC7L3 and SRSF1 and identified SRSF1 as an upper stream regulator of LUC7L3, promoting the translation of LUC7L3 protein. These findings highlight the importance of LUC7L3 in maintaining genome stability and its relationship with SRSF1 in this regulatory pathway.

Retrospective study about clinical severity and epidemiological analysis of the COVID-19 Omicron subvariant lineage-infected patients in Hohhot, China.

BACKGROUND: Fear of a global public health issue and fresh infection wave in the persistent COVID-19 pandemic has been enflamed by the appearance of the novel variant Omicron BF.7 lineage. Recently, it has been seeing the novel Omicron subtype BF.7 lineage has sprawled exponentially in Hohhot. More than anything, risk stratification is significant to ascertain patients infected with COVID-19 who the most need in-hospital or in-home management. The study intends to understand the clinical severity and epidemiological characteristics of COVID-19 Omicron subvariant BF.7. lineage via gathering and analyzing the cases with Omicron subvariant in Hohhot, Inner Mongolia. METHODS: Based upon this, we linked variant Omicron BF.7 individual-level information including sex, age, symptom, underlying conditions and vaccination record. Further, we divided the cases into various groups and assessed the severity of patients according to the symptoms of patients with COVID-19. Clinical indicators and data might help to predict disadvantage outcomes and progression among Omicron BF.7 patients. RESULTS: In this study, in patients with severe symptoms, some indicators from real world data such as white blood cells, AST, ALT and CRE in patients with Omicron BF.7 in severe symptoms were significantly higher than mild and asymptomatic patients, while some indicators were significantly lower. CONCLUSIONS: Above results suggested that the indicators were associated with ponderance of clinical symptoms. Our survey emphasized the value of timely investigations of clinical data obtained by systemic study to acquire detailed information.

Persistence of antibodies 5 years after hepatitis B vaccination in preterm birth children: A retrospective cohort study using real-world data.

Previous studies did not provide substantial evidence for long-term immune persistence after the hepatitis B vaccine (HepB) in preterm birth (PTB) children. Consequently, there is ongoing controversy surrounding the booster immunization strategy for these children. Therefore, we conducted a retrospective cohort study to evaluate the disparities in immune persistence between PTB children and full-term children. A total of 1027 participants were enrolled in this study, including 505 PTB children in the exposure group and 522 full-term children in the control group. The negative rate of hepatitis B surface antibody (HBsAb) in the PTB group was significantly lower than that in the control group (47.9% vs. 41.4%, p = .035). The risk of HBsAb-negative in the exposure group was 1.5 times higher than that in the control group (adjusted odds ratio [aOR] = 1.5, 95% confidence interval [CI]: 1.1-2.0). The geometric mean concentration (GMC) of HBsAb was much lower for participants in the exposure group compared to participants in the control group (9.3 vs. 12.4 mIU/mL, p = .029). Subgroup analysis showed that the very preterm infants (gestational age <32 weeks) and the preterm low birth weight infants (birth weight <2000 g) had relatively low GMC levels of 3.2 mIU/mL (95% CI: 0.9-11.1) and 7.9 mIU/mL (95% CI: 4.2-14.8), respectively. Our findings demonstrated that PTB had a significant impact on the long-term persistence of HBsAb after HepB vaccination. The very preterm infants (gestational age <32 weeks) and the preterm low birth weight infants (birth weight <2000 g) may be special populations that should be given priority for HepB booster vaccination.

SCML2 contributes to tumor cell resistance to DNA damage through regulating p53 and CHK1 stability.

SCML2 has been found to be highly expressed in various tumors. However, the extent to which SCML2 is involved in tumorigenesis and cancer therapy is yet to be fully understood. In this study, we aimed to investigate the relationship between SCML2 and DNA damage response (DDR). Firstly, DNA damage stabilizes SCML2 through CHK1-mediated phosphorylation at Ser570. Functionally, this increased stability of SCML2 enhances resistance to DNA damage agents in p53-positive, p53-mutant, and p53-negative cells. Notably, SCML2 promotes chemoresistance through distinct mechanisms in p53-positive and p53-negative cancer cells. SCML2 binds to the TRAF domain of USP7, and Ser441 is a critical residue for their interaction. In p53-positive cancer cells, SCML2 competes with p53 for USP7 binding and destabilizes p53, which prevents DNA damage-induced p53 overactivation and increases chemoresistance. In p53-mutant or p53-negative cancer cells, SCML2 promotes CHK1 and p21 stability by inhibiting their ubiquitination, thereby enhancing the resistance to DNA damage agents. Interestingly, we found that SCML2A primarily stabilizes CHK1, while SCML2B regulates the stability of p21. Therefore, we have identified SCML2 as a novel regulator of chemotherapy resistance and uncovered a positive feedback loop between SCML2 and CHK1 after DNA damage, which serves to promote the chemoresistance to DNA damage agents.

Effectiveness of a booster dose of COVID-19 vaccines during an outbreak of SARS-CoV-2 Omicron BA.2.2 in China: A case-control study.

Real-world evidence on the effectiveness of COVID-19 vaccines marketed in China against the Omicron BA.2.2 variant remains scarce. A case-control study was conducted to estimate the vaccine effectiveness (VE) of COVID-19 vaccines marketed in China (inactivated vaccines, an Ad5-nCoV vaccine, and a recombinant protein vaccine). There were 414 cases infected with SARS-CoV-2 and 828 close contacts whose test results were consecutively negative as controls during the outbreak of the Omicron variant in Lu'an City, Anhui Province, China, in April 2022. The overall adjusted VE against Omicron BA.2.2 variant infection in the vaccinated group with any COVID-19 vaccine was 35.0% (95% CI: -9.1-61.3%), whereas the adjusted VE for booster vaccination was 51.6% (95% CI: 15.2-72.4%). Subgroup analysis showed that the overall adjusted VE of the Ad5-nCoV vaccine (65.8%, 95% CI: 12.8-86.6%) during the outbreak while any dose of inactivated vaccines and recombinant protein vaccine offered no protection. The adjusted VE of three-dose inactivated vaccines was 48.0% (95% CI: 8.0-70.6%), and the two-dose Ad5-nCoV vaccine was 62.9% (95% CI: 1.8-86%). There is no protection from a three-dose recombinant protein vaccine. COVID-19 vaccines offered 46.8% (95% CI: 9.5-68.7%) protection from infection within six months. There were statistically significant differences between the VEs of heterologous booster (VE = 76.4%, 95% CI: 14.3-93.5%) and homologous booster vaccination (VE = 51.8%, 95% CI: 9.6-74.3%) (P = .036). Booster vaccination of COVID-19 vaccines offered more protection than full vaccination. A booster vaccination campaign for a booster dose after three doses of a recombinant protein vaccine must be urgently conducted.

A comparative study of the clinical characteristics of spotted fever and severe fever with thrombocytopenia syndrome / 中国热带医学

@#Abstract: Objective To investigate the differences in epidemiological and clinical characteristics of patients with spotted fever (SF) and severe fever with thrombocytopenia syndrome (SFTS). Methods A total of 86 patients with SF and 113 patients with SFTS who were laboratory-confirmed in the second-level and above hospitals in Lu'an City from January 2017 to January 2022 were selected. The basic data, epidemiological history, clinical data and laboratory test results of the two diseases were retrospectively analyzed for comparison. Results The proportion of male in SF group was 32.56% (28/86), and the proportion of male in SFTS group was 53.98% (61/113), the difference was statistically significant (χ2=9.067, P<0.01). The proportions of abdominal pain and diarrhea in the SF group were (3.49%, 3/83) and (21.24%, 24/113), which were significantly lower than corresponding (6.98%, 6/86) and (46.90%, 53/113) in the SFTS group (χ2=13.121, 37.322, P<0.01). The incidences of rash and eschar in SF group were 95.35% (82/86) and 20.93% (18/86), which were significantly higher than corresponding 1.77% (2/113) and 0.88% (1/113) in SFTS group (χ2=175.311, 22.721, P<0.01). The levels of leukocytes, platelets and C-reactive protein in the SF group were significantly higher than those in the SFTS group, and the levels of transaminase, lactate dehydrogenase and D-dimer were significantly lower than those in the SFTS group, and the differences were statistically significant (all P<0.05). Conclusions The rash and inflammatory reaction are more obvious in SF patients, while the liver function, myocardial function and coagulation function are significantly impaired in SFTS patients.

A retrospective study of hepatitis B vaccination in preterm birth and low birth weight infants born to hepatitis B surface antigen-positive mothers: Time to close the policy-practice gap.

National Immunization Program-version 2016 (ISIV-NIP-v2016) recommended a 4-dose hepatitis B vaccine (HepB) schedule for preterm birth (PTB) and low birth weight (LBW) infants born to HBsAg-positive mothers. However, the implementation of this immunization strategy in the past five years has not been fully evaluated in China. We reviewed the data of pregnant women and live-born infants from 24 hospitals between 2016 and 2021 in Lu'an, Anhui province, to estimate the prevalence of PTB, LBW, and hepatitis B virus (HBV) infected pregnant women. We analyzed the vaccination status of HepB and HBIG among PTB and LBW infants born to HBsAg-positive mothers. A total of 160 222 pregnant women and 159 613 live-born infants were included in this study. The estimated prevalence of PTB, LBW and HBV-infected pregnant women was 3.86% (range: 3.28%-5.10%), 2.77% (range: 2.12%-3.66%), and 3.27% (range: 3.03%-3.49%), respectively. We screened 340 PTB and LBW infants born to HBsAg-positive mothers between 2016 and 2020. We found that the coverage of HepB and HBIG among them was 100% and 99.39%. However, the timely vaccination rate of the HepB birth dose was only 78.59% and only four children (1.22%) received the 4-dose HepB as recommended by ISIV-NIP-v2016. The 4-dose of HepB for PTB and LBW infants born to HBsAg-positive mothers recommended by ISIV-NIP-v2016 was not fully implemented. A strong public health intervention should be taken to close the policy-practice gap in China in the future.

The acceptance to heterologous booster vaccination of COVID-19 vaccine among HCWs and targeted population: A cross-sectional study in central China.

Background: There are few studies reported on the acceptance of heterologous booster vaccination for the COVID-19 vaccine among healthcare workers (HCWs) and the general population. We aimed to address that gap and explore determinant factors of acceptance of the heterologous booster vaccination. Methods: We conducted a cross-sectional study to examine the prevalence and determinant factors of the acceptance of heterologous booster vaccination for the COVID-19 vaccine among HCWs and the targeted population. Results: A total of 364 HCWs and 1,898 targeted populations were investigated in our study. 76.4% HCWs would recommend heterologous booster vaccination to their patients and 59.8% targeted population endorsed a clear willingness to receive this strategy. Compared with the adenoviral vector vaccine (AD5-nCOV), recombinant protein vaccine (ZF2001) was more preferred by HCWs (79.1%) and the targeted population (72.0%) as a heterologous booster vaccine. HCWs who did not work in the vaccination clinics were more likely to recommend heterologous booster vaccination (OR = 3.3, CI: 1.5-7.3). The targeted population aged 18-59 years (OR = 1.5, 95% CI:1.1-2.3), had a positive attitude toward COVID-19 vaccination (OR = 3.8, 95% CI: 1.7-8.6), had confidence in the safety of COVID-19 vaccines (OR = 6.6, 95% CI: 4.2-10.2), followed the recommendation of HCWs (OR = 33.6, 95% CI: 22.0-51.2), took initiative in collecting booster shots information (OR = 2.1, 95% CI: 1.5-3.0), and were familiar with the heterologous strategy (OR = 1.9, 95% CI: 1.1-3.1) were more likely to choose heterologous booster vaccination. The history of side effects of inactivated COVID-19 vaccine was a negative factor in choosing heterologous booster vaccination (OR = 0.4, 95% CI: 0.4-1.0). Conclusions: The heterologous booster vaccination strategy on the COVID-19 vaccine could be widely accepted among HCWs, whereas its acceptance among targeted population was only moderate. Public authorities should make efforts to communicate the public about the effectiveness and safety of the heterologous booster vaccination which could help increase their willingness to get vaccinated.

Transcutaneous Electrical Acupoint Stimulation Decreases the Incidence of Postoperative Nausea and Vomiting After Laparoscopic Non-gastrointestinal Surgery: A Multi-Center Randomized Controlled Trial.

Importance: Postoperative nausea and vomiting (PONV) gives patients a bad experience and negates their good recovery from surgery. Objective: This trial aims to assess the preventive effectiveness of transcutaneous electrical acupoint stimulation (TEAS) on the incidence of PONV in high-risk surgical patients. Design: The large sample size, multicenter, evaluator-blinded, and randomized controlled study was conducted between September 3, 2019 to February 6, 2021. Setting: The 12 hospitals were from different Chinese provinces. Participants: After obtaining ethics approval and written informed consent, 1,655 patients with Apfel score ≥ 3 points were enrolled for selective laparoscopic non-gastrointestinal surgery under general anesthesia. Interventions: Patients were randomly allocated into the TEAS and Sham group with a 1:1 ratio. The TEAS group was stimulated on bilateral Neiguan and Zusanli acupoints after recovery from anesthesia on the surgical day and the next morning for 30 min, while the Sham group received an identical setting as TEAS but without currents delivered. Electronic patient self-reported scale was used to evaluate and record the occurrence of PONV. Main Outcomes and Measures: Primary clinical end point is the incidence of PONV which was defined as at least one incidence of nausea, retching, or vomiting after operation within postoperative 24 h. Results: Compared with the Sham treatment, the TEAS lowered the PONV incidence by 4.8% (29.4 vs. 34.2%, P = 0.036) and vomiting incidence by 7.4% (10.4 vs. 17.8%, P < 0.001). TEAS also lowered persistent nausea incidence and PONV scores and decreased PONV related complications and Quality of Recovery-40 scores (P < 0.05). TEAS lowered the 24 h PONV risk by 20% (OR, 0.80, 95% CI, 0.65 -0.98; P = 0.032), and lowered hazard ratio by 17% (HR, 0.83, 95% CI, 0.70-0.99; P = 0.035). Both TEAS and palonosetron were the independent PONV risk protective factors for 24 h PONV incidence and cumulative PONV incidence. The combination of TEAS and palonosetron was the most effective strategy to reduce the PONV incidence (P < 0.001). Conclusions and Relevance: TEAS attenuated the PONV incidence and severity in high-risk surgical patients and may be applied clinically as a complement therapy to prevent PONV. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04043247, identifier: NCT04043247.

Recurrence of sigmoid colon cancer-derived anal metastasis: A case report and review of literature.

BACKGROUND: Distant metastasis of colorectal cancer to the anus is very rare, with only 30 related cases published in PubMed thus far. Therefore, recurrence of colorectal cancer derived anus metastases is rarely seen and less presented. CASE SUMMARY: Here we report an 80-year-old male patient who underwent radical resection for sigmoid colon cancer in January 2010 and another surgery for anal fistula resection in December 2010. Postoperative pathology of the anal fistula revealed a metastatic moderately differentiated adenocarcinoma. The patient subsequently received chemotherapy and radiotherapy. In May 2020, after the patient reported symptoms of anal swelling and pain, computed tomography and magnetic resonance imaging revealed a perianal abscess. Perianal mass biopsy was performed, and the postoperative pathological diagnosis was metastatic moderately differentiated adenocarcinoma. CONCLUSION: This case highlights that there is a risk of recurrence of anal metastasis of colorectal cancer even after 10 years of follow-up. We also reviewed the literature and discuss potential mechanisms for anal metastasis of colorectal cancer, thus providing some suggestions for treatment of these cases.

Malignant transformation of perianal tailgut cyst: A case report.

BACKGROUND: Tailgut cyst is a congenital enterogenous cyst that rarely undergoes malignant transformation. Its clinical manifestations mainly correlate to the mass effect caused by the development of cysts and the infections that originate from these. Furthermore, the complete resection of this cyst is curative. We report our diagnostic and treatment experience with one case of malignant transformation of a perianal tailgut cyst, which was initially misdiagnosed as perianal abscess. CASE SUMMARY: A 72-year-old woman visited our institution with complaints of a refractory nonhealing lesion on the right hip, which repeatedly broke and suppurated for more than 70 years, and aggravated in 4 mo. The patient was given a diagnosis of refractory perianal abscess with repeated incision and drainage procedures. Computed tomography of the pelvic cavity revealed a giant perianal cyst. Subsequent biopsy revealed a tumor with moderate-to-severe glandular epithelial dysplasia, and suggested that this was derived from the developmental cysts in the posterior rectal space. After further clarifying the nature and extent of the tumor by magnetic resonance imaging, total cystic resection was performed. Postoperative histopathological examination confirmed the malignancy, dictating the investigators to add postoperative chemotherapy to the treatment regimen. CONCLUSION: The malignant transformation of perianal tailgut cysts is very uncommon, and this should be differentiated from perianal abscess. Complete surgical removal is curative, and postoperative pathology may determine the necessity of additional postoperative chemotherapy or radiotherapy, which may be beneficial for preventing local recurrence and metastasis.

C-Phycocyanin elicited antitumor efficacy via cell-cycle arrest, apoptosis induction, and invasion inhibition in esophageal squamous cell carcinoma.

Objectives: Mounting evidence has demonstrated that C-Phycocyanin (C-PC) exhibits marked antitumor activity in a wide type of tumors, such as pancreas cancer, breast carcinoma, lung cancer, and colon cancer. The current study aimed to confirm the antitumor efficacy of C-PC in esophageal squamous cell carcinoma (ESCC). Methods: The efficacy of C-PC was evaluated against the proliferation of ESCC cell lines EC9706 and EC1 by CCK-8 kit and in a mice model of ESCC EC9706. Cell cycle and apoptosis were investigated by flow cytometry, and cell invasion was determined via transwell chamber. Protein expression was examined by Western blots. Results: We found that C-PC exhibited anti-proliferation ability in a time-dependent manner and a dose-dependent manner in ESCC EC9706 and EC1 cells. Besides, C-PC markedly arrested cell cycle in the G0/G1 phase, induced cell apoptosis and suppressed cell invasion ability in both EC9706 and EC1 cells (p < .01). Notably, C-PC evoked the elevations of Bax, PARP, and cleaved-caspase-3 protein, but reduced cyclin D1, CDK4, Bcl-2, MMP-2, and MMP-9 expression levels. Further investigation from in vivo experiment revealed that C-PC displayed significant antitumor efficacy in the xenografted EC9706 model. Conclusions: Our data presented herein suggest C-PC exerts antitumor efficacy in ESCC.

MicroRNA-125a-5p enhances the sensitivity of esophageal squamous cell carcinoma cells to cisplatin by suppressing the activation of the STAT3 signaling pathway.

Increasing evidence has demonstrated that microRNAs (miRNAs or miRs) play a variety of roles in tumor development, progression and chemosensitivity in a wide range of tumors. In this study, we found that miR­125a­5p exhibited a low expression in esophageal squamous cell carcinoma (ESCC) tissues and cells, and that its low expression was associated with higher tumor staging and shorter a survival time of patients with ESCC. Moreover, miR­125a­5p overexpression contributed to the suppression of cell proliferation, cell cycle arrest, cell apoptosis and a decrease in cell migratory and invasive abilities, whereas the downregulation of miR­125a­5p promoted cell proliferation, accelerated cell cycle progression, suppressed apoptosis and enhanced the migratory and invasive abilities of ESCC EC1 and TE1 cells, which may be tightly associated with the epithelial­mesenchymal transition (EMT) process in ESCC. Importantly, miR­125a­5p enhanced the cytotoxic effects of cisplatin on EC1 and TE1 cells, and co­treatment with miR­125a­5p and cisplatin significantly induced cell apoptosis and reduced the cell migratory and invasive abilities of EC1 and TE1 cells, coupled with an increase in the E­cadherin level and a decrease in the N­cadherin and Vimentin levels. Most notably, signal transducer and activator of transcription­3 (STAT3) was found to be a direct target of miR­125a­5p in ESCC cells, and miR­125a­5p overexpression significantly reduced the protein levels of t­STAT3, p­STAT3 and vascular endothelial growth factor (VEGF) in EC1 and TE1 cells. Furthermore, the combination of miR­125a­5p and cisplatin markedly inactivated the STAT3 signaling pathway; however, interleukin (IL)­6, a widely reported activator of the STAT3 signaling pathway, reversed the suppressive effects of miR­125a­5p/cisplatin in ESCC cells on the activation of the STAT3 signaling pathway. Of note, we found that IL­6 markedly reversed the altered cell phenotype mediated by the combination of miR­125a­5p and cisplatin in ESCC cells. These findings suggest that miR­125a­5p may play a pivotal role in the development and progression of ESCC, which may be achieved via the manipulation of the STAT3 signaling pathway.

MicroRNA-16-5p overexpression suppresses proliferation and invasion as well as triggers apoptosis by targeting VEGFA expression in breast carcinoma.

MicroRNAs (miRNAs), a class of small noncoding RNA molecules, can manipulate the expressions of endogenous tumor-related genes, and are implicated in the development and progression of a wide type of tumors. In this study, the investigation from real-time quantitative PCR revealed that miRNA-16-5p was downregulated in breast carcinoma tissues and cells, coupled with the elevations of HIF-α and VEGFA protein expressions, compared with normal tissues. Lentiviral armed with miR-16-5p markedly increased the miR-16-5p levels in MCF-7 and MDA-MB-231 cells, compared to blank and NC groups, and miR-16-5p overexpression significantly inhibited the proliferation and colony formation in MCF-7 and MDA-MB-231 cells. Besides, miR-16-5p upregulation markedly induced apoptosis and reduced invasion ability in MCF-7 and MDA-MB-231 cells. Notably, VEGFA was direct target of miR-16-5p. Stepwise investigation from in vitro and in vivo experiments demonstrated that miR-16-5p overexpression suppressed tumor growth and reduced HIF-α and VEGFA expressions in breast carcinoma cells and nude mice tumor tissues. These findings provide novel insights into molecular mechanism involved in the roles of miR-16-5p in tumor development and progression of breast carcinoma, and thus manipulation of miR-16-5p may be a novel potential therapeutic target for future therapies of the patients with breast carcinoma.

Preliminary evaluation for Bit1 as a potential biomarker for squamous cell carcinoma and adenocarcinoma of esophagus.

Mounting evidence has demonstrated that Bit1 has been investigated as an etiological factor for certain cancers, including esophageal squamous cell carcinoma reported in our previous study, but data regarding possible roles of Bit1 in esophageal squamous cell carcinoma and esophageal adenocarcinoma remain to be elucidated. The purpose of this study was to examine whether Bit1 can be a novel diagnostic marker for the patients with esophageal squamous cell carcinoma and esophageal adenocarcinoma. The results revealed that Bit1 level in esophageal squamous cell carcinoma was significantly higher than that in esophageal adenocarcinoma tissues ( p < 0.05); notably, Bit1 level in esophageal adenocarcinoma tissues was lower than that in paired normal tissues but no difference was found ( p > 0.05). Bit1 expression patterns were completely in accordance with matrix metalloproteinase 2 and Bcl-2 in esophageal squamous cell carcinoma and esophageal adenocarcinoma. In addition, Bit1, Bcl-2, and matrix metalloproteinase 2 expression patterns in different differentiated esophageal squamous cell carcinoma were higher than those in corresponding normal esophageal tissues. Bit1 expression in poorly differentiated esophageal squamous cell carcinoma was significantly higher than that in normal esophageal tissues ( p < 0.05) but not in moderately and well-differentiated esophageal squamous cell carcinoma. Matrix metalloproteinase 2 expression patterns in poorly and moderately differentiated esophageal squamous cell carcinoma were significantly higher than those in corresponding normal esophageal tissues ( p < 0.01) but not in well-differentiated esophageal squamous cell carcinoma tissue ( p > 0.05). Bcl-2 expression patterns in various differentiated esophageal squamous cell carcinoma were higher than those in corresponding normal esophageal tissues with no statistical differences ( p > 0.05). Importantly, Bit1 expression was positively correlated with both matrix metalloproteinase 2 and Bcl-2 expression in esophageal squamous cell carcinoma and esophageal adenocarcinoma tissues ( p < 0.05). Collectively, these preliminary data support further investigation of Bit1 as an important diagnostic factor for esophageal squamous cell carcinoma and esophageal adenocarcinoma.

Molecular cloning and nutrient regulation analysis of long chain acyl-CoA synthetase 1 gene in grass carp, Ctenopharyngodon idella L.

Long chain acyl-CoA synthetase 1 (ACSL1), a key regulatory enzyme of fatty acid metabolism, catalyzes the conversion of long-chain fatty acids to acyl-coenzyme A. The full-length cDNAs of ACSL1a and ACSL1b were cloned from the liver of a grass carp. Both cDNAs contained a 2094bp open reading frame encoding 697 amino acids. Amino acid sequence alignment showed that ACSL1a shared 73.5% sequence identity with ACSL1b. Each of the two ACSL1s proteins had a transmembrane domain, a P-loop domain, and L-, A-, and G-motifs, which were relatively conserved in comparison to other vertebrates. Relative expression profile of ACSL1 mRNAs in different tissues indicated that ACSL1a is highly expressed in heart, mesenteric adipose, and brain tissues, whereas ACSL1b is highly expressed in heart, white muscle, foregut, and liver tissues. Nutrient regulation research showed that the expression levels of ACSL1a and ACSL1b were significantly down-regulated when 3, 6, and 9% fish oil were added in diet of grass carp as compared to the control group. However, no significant difference in the levels of ACSL1 mRNA was observed between the experimental groups. This study demonstrated the relationship between ACSL1a and ACSL1b genes in grass carp and laid a foundation for further research on ACSL family members in other species.

Bit1 knockdown contributes to growth suppression as well as the decreases of migration and invasion abilities in esophageal squamous cell carcinoma via suppressing FAK-paxillin pathway.

BACKGROUND: There is growing evidence that Bit1 exerts different roles in the development and progression of human cancers. Although Bit1 was highly exhibited in ESCC tissues in our previous study, its roles and molecular mechanisms implicated in development and progression of ESCC remain unknown. METHODS: Bit1 protein expression in ESCC cell lines and normal esophageal epithelial cell was detected by Western blotting. Bit1 protein expression mediated by Bit1 shRNA was investigated by Western blotting. MTT, migration assay, invasion experiment, ELISA and Flow cytometry were utilized to determine the effects of Bit1 knockdown on cell proliferation, migration, invasion and apoptosis, respectively. A xenograft model was used to examine in vivo tumourigenicity, and immunohistochemistry and TUNEL were utilized to evaluate the related protein expression and apoptosis. Gene microarray was determined by Agilent SurePrint G3 Human GE 8 × 60 K Microarray, the interaction of Bit1 and FAK proteins were detected by Immunoprecipitation and the key protein expressions of FAK-paxillin pathway were detected by Western blotting. RESULTS: We found Bit1 expression in all human ESCC cell lines tested was significantly higher than that in normal esophageal epithelial cell Het-1A (P < 0.05), in which EC9706 presented the highest Bit1 level. Bit1 protein level was significantly downregulated at day 1 after transfection with specific shRNA against Bit1 (P < 0.05). At days 2 and 3, Bit1 level reached the lowest value after transfection with Bit1 shRNA. Moreover, Bit1 depletion contributed to growth inhibition in vitro and in vivo, reduced cell migration and invasion abilities, and induced cell apoptosis in EC9706 and TE1 cells. More importantly, Bit1 downregulation significantly lowered Bcl-2 and MMP-2 levels in EC9706 xenografted tumor tissues, meanwhile triggered apoptosis after treatment with different doses of Bit1 shRNA. Further gene microarray revealed that 23 genes in Bit1-RNAi group were markedly downregulated, whereas 16 genes were obviously upregulated. Notably, Bit1 intrinsically interacted with FAK protein in EC9706 cells. Moreover, paxillin was downregulated at mRNA and protein levels in Bit1 shRNA group, coupled with the decreases of FAK mRNA and protein expressions. CONCLUSION: Bit1 may be an important regulator in cell growth, apoptosis, migration and invasion of ESCC via targeting FAK-paxillin pathway, and thereby combinative manipulation of Bit1 and FAK-paxillin pathway may be the novel and promising therapeutic targets for the patients with ESCC.

G6PD downregulation triggered growth inhibition and induced apoptosis by regulating STAT3 signaling pathway in esophageal squamous cell carcinoma.

There is growing evidence that glucose-6-phosphate dehydrogenase (G6PD) is tightly associated with development and progression of many human tumors. However, its precise molecular mechanisms in esophageal squamous cell carcinoma (ESCC) remain unknown. In the current study, we found that G6PD messenger RNA (mRNA) and protein levels in ESCC cell lines (Eca109, EC1, and EC9706 cells) were significantly higher than that in normal esophageal epithelial cell line Het-1A (P < 0.05) and specific small interfering RNA (siRNA) against G6PD significantly reduced the levels of G6PD mRNA and protein in EC1 cells with highest G6PD levels (P < 0.05). Further investigation revealed that G6PD depletion contributed to the growth suppression in EC1 cells in vitro and EC1 cells xenografted nude mice in vivo, which was associated with the reduces of tumor weight and Ki-67 proliferation index, triggered cell cycle arrest at G0/G1 phase coupled with obvious decreases of cyclin D1 and CDK4 protein levels, and induced cell apoptosis accompanied by the increases of caspase-3 activity and Bax protein expression as well as the decrease of Bcl-2 protein expression in EC1 cells. More importantly, G6PD depletion significantly reduced the level of p-STAT3 protein but did not alter total STAT3 protein level. Taken altogether, our data presented herein suggest that G6PD may function as an important regulator in development and progression of ESCC by manipulating STAT3 signaling pathway and thus may be an underlying molecular target for therapy of the patients with ESCC.

Glucose-6-phosphate dehydrogenase expression is correlated with poor clinical prognosis in esophageal squamous cell carcinoma.

Increasing evidence has demonstrated that glucose-6-phosphate dehydrogenase (G6PD), a key metabolic enzyme, participating in pentose phosphate pathway (PPP), is tightly associated with development and progression of a variety of tumors. Here, we reported expression of G6PD and its association with the prognosis of the patients with esophageal squamous cell carcinoma (ESCC). The results revealed significantly elevated G6PD mRNA and protein expressions in ESCC tissues compared with normal tissues (P < 0.05). Furthermore, high G6PD expression was tightly associated with histological grade, TNM staging and lymph node metastasis (P < 0.05), but not related to the patients' age and gender (P > 0.05). Importantly, the survival time of G6PD-positive patients was markedly lower than that of G6PD-negative patients (P < 0.05). Most notably, Cox multivariate assay demonstrated that G6PD was an independent prognostic factor for the patients with ESCC. In conclusion, G6PD may be a novel predictor for the prognosis of the patients with ESCC.