PANoptosis subtypes predict prognosis and immune efficacy in gastric cancer.

PANoptosis is a form of inflammatory programmed cell death that is regulated by the PANoptosome. This PANoptosis possesses key characteristics of pyroptosis, apoptosis, and necroptosis, yet cannot be fully explained by any of these cell death modes. The unique nature of this cell death mechanism has garnered significant interest. However, the specific role of PANoptosis-associated features in gastric cancer (GC) is still uncertain. Patients were categorized into different PAN subtypes based on the expression of genes related to the PANoptosome. We conducted a systematic analysis to investigate the variations in prognosis and tumor microenvironment (TME) among these subtypes. Furthermore, we developed a risk score, called PANoptosis-related risk score (PANS), which is constructed from genes associated with the PANoptosis. We comprehensively analyzed the correlation between PANS and GC prognosis, TME, immunotherapy efficacy and chemotherapeutic drug sensitivity. Additionally, we performed in vitro experiments to validate the impact of Keratin 7 (KRT7) on GC. We identified two PAN subtypes (PANcluster A and B). PANoptosome genes were highly expressed in PANcluster A. PANcluster A has the characteristics of favorable prognosis, abundant infiltration of anti-tumor lymphocytes, and sensitivity to immunotherapy, thus it was categorized as an immune-inflammatory type. Meanwhile, our constructed PANS can effectively predict the prognosis and immune efficacy of GC. Patients with low PANS have a good prognosis, and have the characteristics of high tumor mutation load (TMB), high microsatellite instability (MSI), low tumor purity and sensitivity to immunotherapy. In addition, PANS can also identify suitable populations for different chemotherapy drugs. Finally, we confirmed that KRT7 is highly expressed in GC. Knocking down the expression of KRT7 significantly weakens the proliferation and migration abilities of GC cells. The models based on PANoptosis signature help to identify the TME features of GC and can effectively predict the prognosis and immune efficacy of GC. Furthermore, the experimental verification results of KRT7 provide theoretical support for anti-tumor treatment.

An immunogenic cell death-related signature predicts prognosis and immunotherapy response in stomach adenocarcinoma.

The immunogenic cell death (ICD) is a specific type of regulatory cell death (RCD), which induces adaptive immunity against antigens of dead cells. ICDs have received increasing attention for their potential role in tumor microenvironment reprogramming and immunotherapy. However, the relationship between ICD-related features and stomach adenocarcinoma (STAD) prognosis, immune cell infiltration and immunotherapy remains unclear. Patients were divided into different ICD-related subtypes by consensus clustering. The differences in prognosis, Tumor microenvironment (TME), and immune checkpoint expression between different ICD-related subtypes were systematically assessed. Additionally, we constructed an ICD-related gene risk score (ICDRS). We systematically analyzed the correlation between ICDRS and prognosis, TME, immunotherapy response and drug sensitivity of gastric cancer. In addition, we explored the role of TGM2 in promoting gastric cancer progression through in vitro experiments. We identified three ICD-associated subtypes by consensus clustering. The ICD gene was highly expressed in Cluster B. Compared with the other two subtypes, Cluster B had better prognosis, higher immune response signaling activity, massive immune cell infiltration and lower tumor purity. Immune checkpoint (ICP) and human leukocyte antigen (HLA) related genes were also highly expressed in Cluster B. In addition, we found that ICDRS is an effective indicator for predicting the prognosis and immune efficacy of STAD. The low ICDRS group has the characteristics of good prognosis, high tumor mutation burden (TMB), high microsatellite instability (MSI), and sensitivity to immunotherapy, while the high ICDRS group is prone to immune escape and immunotherapy resistance. In addition, we found that down-regulating TGM2 gene can inhibit the proliferation and migration of gastric cancer cells through in vitro experiments. Our study found that the model based on ICD features is helpful to clarify the TME characteristics of STAD, and has important clinical significance for evaluating the prognosis and immunotherapy response of STAD patients. TGM2 plays an important role in the progression of STAD, suggesting that TGM2 can be used as a new target for the treatment of STAD.

Impact of primary tumor resection on the survival of patients with unresectable colon cancer liver metastasis at different colonic subsites: a propensity score matching analysis.

OBJECTIVE: To investigate the effect of primary tumor resection (PTR) on the prognosis of patients with unresectable colon cancer liver metastasis (UCCLM) at seven colonic subsites using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Propensity score matching (PSM) was performed to balance selection bias using all available variables that could be of potential relevance. After matching, the groups were redefined in a 1:1 ratio using the nearest method. Cancer-specific survival (CSS) was compared among the patients of PTR and non-PTR groups. Cox regression models were used to identify the prognostic factors for CSS. RESULTS: CSS was significantly different between all groups. Cox regression analysis showed that PTR was an independent prognostic factor for all groups. After PSM, PTR significantly prolonged CSS for all groups. Subgroup analysis showed that PTR did not improve the prognosis of N2 stage patients in the cecum, ascending colon, and descending colon groups; T1 + T2 stage patients in the hepatic flexure group; and patients with a tumor size ≤5 cm in the splenic flexure group. Segmental colectomy could prolong CSS of patients in the cecum, ascending colon, transverse colon, splenic flexure, and sigmoid colon groups, while extended colectomy could prolong CSS of patients in the hepatic flexure and descending colon groups. CONCLUSION: At different colonic subsites, UCCLM patients had different CSS. PTR could improve their prognosis, however, N stage, T stage, and tumor size are important reference indicators. In addition to patients in the hepatic flexure and descending colon groups, we suggested that patients in other groups should choose segmental colectomy.

Revealing novel synergistic defense and acid tolerant performance of Escherichia coli in response to organic acid stimulation.

Escherichia coli is an important producer of mono- and di-acids, such as D-lactic acid, itaconic acid, and succinic acid. However, E. coli has limited acid tolerance and requires neutralizers in large-scale fermentation, which leads to increased production costs. Mutagenesis breeding has been shown to be inefficient in improving the acid tolerance of strains. Therefore, it is crucial to analyze the acid resistance mechanism of E. coli. To this end, important regulatory genes and metabolic pathways in the highly evolved acid-resistant E. coli were identified based on transcriptome sequencing. By analyzing the overlap of the genes with significantly different expression levels in the four groups, a synergistic membrane-centric defense mechanism for E. coli against organic acid stress was identified. The mechanism includes four modules: signal perception, energy countermeasures, input conditioning, and envelope reinforcement. In addition, genes related to the ABC transporter pathway, polyketide metabolism, pyrimidine metabolism, and dual-arginine translocation system pathways were found for the first time to be potentially resistant to organic acid stress after overexpression. A new antacid ingredient, RffG, increases the survival rate of E. coli by 4509.6 times. This study provides new clues for improving the performance of acid-tolerant cells and reducing the production cost of industrial organic acid fermentation. KEY POINTS: • Systematic analysis of the mechanism of membrane protein partitioning in E. coli to resist organic acids • TAT system transports correctly folded hydrogenase accessory proteins to resist D-lactic acid stress • Enhanced PG synthesis and weakened hydrolysis to reduce acid penetration into cells • Overexpression of RffG in the polyketide synthesis pathway enhances acid tolerance.

Complete Genome Sequencing Analysis of Deinococcus wulumuqiensis R12, an Extremely Radiation-Resistant Strain.

Genome sequencing was performed by the PacBio RS II platform and Illumina HiSeq 4000 platform to discover the metabolic profile of the Deinococcus wulumuqiensis R12, which was isolated from radiation-contaminated soils in Xinjiang Uygur Autonomous Region of northwest China. The genome of 3.5 Mbp comprises one circular chromosome and four circular plasmids with 3679 genes and a GC content of 66.97%. A total of 41 new transcriptional factors were identified using the DeepTFactor tool. Genomic analysis revealed the presence of genes for homologous recombination repair, which suggested high recombination efficiency in R12. Three Type I and one Type II RM systems, two CRISPR arrays, and one Cas-Type IC protein were found, allowing the development of endogenous CRISPR-Cas gene-editing tools. Additionally, we found that R12 has a broad spectrum of substrate utilization, which was validated by physiological experiments. Genes involved in the carotenoid biosynthesis pathway and the antioxidative system were also identified. Overall, the comprehensive description of the genome of R12 will facilitate the additional exploitation of this strain as a versatile cell factory for biotechnological applications.

Primary tumor resection improves prognosis of unresectable carcinomas of the transverse colon including flexures with liver metastasis: a preliminary population-based analysis.

PURPOSE: Studies on unresectable colorectal cancer liver metastasis(CRLM) rarely analyze the prognosis of the patients from the point of colonic subsites. We aimed to evaluate the effect of primary tumor resection (PTR) and different scope of colectomy on the prognosis of patients with unresectable transverse colon cancer liver metastasis (UTCLM), hepatic flexure cancer liver metastasis (UHFLM), and splenic flexure cancer liver metastasis (USFLM). PATIENTS AND METHODS: The patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Cox proportional hazards regression models were used to identify prognostic factors of overall survival (OS) and cause-specific survival (CSS). Kaplan-Meier analyses and log-rank tests were conducted to assess the effectiveness of PTR on survival. RESULTS: In total, this study included a cohort of 1960 patients: 556 cases of UHFLM, 1008 cases of UTCLM, and 396 cases of USFLM. The median survival time of whole patients was 11.0 months, ranging from 7.0 months for UHFLM patients to 15.0 months for USFLM patients. USFLM patients had the best OS and CSS, followed by UTCLM patients. UHFLM patients had the worst OS and CSS (All P < 0.001). PTR could improve the OS and CSS of UTCLM, UHFLM, and USFLM (All P < 0.001). Subgroups analysis revealed that USFLM patients with tumor size≤5 cm and negative CEA had not demonstrated an improved OS and CSS after PTR. Multivariate analysis showed that PTR and perioperative chemotherapy were common independent prognostic factors for UHFLM, UTCLM, and USFLM patients. There was no difference between segmental colon resection and larger colon resection on CSS of UHFLM, UTCLM, and USFLM patients. CONCLUSIONS: We confirmed the different survival of patients with UTCLM, UHFLM, and USFLM, and for the first time, we proved that PTR could provide survival benefits for patients with unresectable CRLM from the perspective of colonic subsites of transverse colon, hepatic flexure, and splenic flexure. Besides, PTR may not improve the prognosis of USFLM patients with CEA- negative or tumor size≤5 cm. For oncologic outcomes, we concluded that segmental colon resection seemed an effective surgical procedure for UTCLM, UHFLM, and USFLM.

TAB3 upregulates PIM1 expression by directly activating the TAK1-STAT3 complex to promote colorectal cancer growth.

Transforming growth factor-ß-activated kinase 1 (TAK1)-binding protein 3 (TAB3) and the proviral integration site for Moloney murine leukaemia virus 1 (PIM1) are implicated in cancer development. In this study, we investigated the relationship between TAB3 and PIM1 in colorectal cancer (CRC) and determined the potential role and molecular mechanism of TAB3 in PIM1-mediated CRC growth. We found that TAB3 and PIM1 expression levels were positively correlated in CRC tissues. The knockdown of TAB3 significantly decreased PIM1 expression and inhibited CRC proliferation in vitro and in vivo. The upregulation of PIM1 rescued the decreased cell proliferation induced by TAB3 knockdown, whereas PIM1 knockdown decreased TAB3-enhanced CRC proliferation. Additionally, TAB3 regulates PIM1 expression through the STAT3 signalling pathway and confirmed a positive correlation between TAB3 and phosphorylated-STAT3 expression in CRC tissues. Patients with high expression of TAB3 and phosphorylated-STAT3 had the worst prognosis. Mechanistically, TAB3 regulates PIM1 expression by promoting STAT3 phosphorylation and activation through the formation of the TAB3-TAK1-STAT3 complex. Overall, a novel CRC regulatory circuit involving the TAB3-TAK1-STAT3 complex and PIM1 was identified, the dysfunction of which may contribute to CRC tumorigenesis.

The challenges and prospects of Escherichia coli as an organic acid production host under acid stress.

OBJECTIVE: Organic acids have a wide range of applications and have attracted the attention of many industries, and their large-scale applications have led fermentation production to low-cost development. Among them, the microbial fermentation method, especially using Escherichia coli as the production host, has the advantages of fast growth and low energy consumption, and has gradually shown better advantages and prospects in organic acid fermentation production. IMPORTANCE: However, when the opportunity comes, the acidified environment caused by the acid products accumulated during the fermentation process also challenges E. coli. The acid sensitivity of E. coli is a core problem that needs to be solved urgently. The addition of neutralizers in traditional operations led to the emergence of osmotic stress inadvertently, the addition of strong acid substances to recover products in the salt state not only increases production costs, but the discharged sewage is also harmful to the environment. ELABORATION: This article summarizes the current status of the application of E. coli in the production of organic acids, and based on the impact of acid stress on the physiological state of cells and the impact of industrial production profits, put forward some new conjectures that can make up for the deficiencies in existing research and application. IMPLICATION: At this point, the diversified transformation of E. coli has become a chassis microbe that is more suitable for industrial fermentation, enhancing industrial application value. KEY POINTS: • E. coli is a potential host for high value-added organic acids production. • Classify the damage mechanism and coping strategies of E. coli when stimulated by acid molecules. • Multi-dimensional expansion tools are needed to create acid-resistant E. coli chassis.

Efficacy and safety of Seprafilm for preventing intestinal obstruction after gastrointestinal neoplasms surgery: a systematic review and meta-analysis.

OBJECTIVE: It was controversial that hyaluronate-carboxy-methylcellulose-based membrane (Seprafilm) could prevent intestinal obstruction after gastrointestinal neoplasms operation. This study aimed to evaluate the efficacy and safety of Seprafilm in preventing postoperative intestinal obstruction of gastrointestinal neoplasms patients. METHODS: A systematic research of multiple databases was performed to identify relevant studies, and the studies satisfying the inclusion criteria were included. Risk ratio (RR), weighted mean difference (WMD), and 95% confidence intervals were calculated using RevMan 5.3. RESULTS: 2937 patients from 10 studies who were enrolled in this meta-analysis were divided into the Seprafilm group (n = 1334) and the control group (n = 1603). The Seprafilm group had lower incidence of intestinal obstruction (RR, 0.52; 95% CI, 0.38-0.70; p < .0001), reoperation rates due to intestinal obstruction (RR, 0.48; 95% CI, 0.28 - 0.80; p = .005), incidence of overall complications (RR, 0.77; 95% CI, 0.61-0.97; p = .03) and higher serum creatinine on postoperative day 5 (WMD, 0.15; 95% CI, 0.05-0.25; p = .003). There were no differences regarding time to intestinal obstruction after operation, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, white blood cell count results on day 5 and 7, serum creatinine on day 7, hospital stay, and incidence of intra-abdominal infection, wound infection, anastomotic leakage between the 2 groups. CONCLUSIONS: This meta-analysis provided valuable evidence-based support for the efficacy and safety of Seprafilm in preventing postoperative intestinal obstruction of gastrointestinal neoplasms patients. However, more multicenter randomized controlled trials from different countries are needed.

Transplantation of microencapsulated neural stem cells inhibits neuropathic pain mediated by P2X7 receptor overexpression.

BACKGROUND: Neuropathic pain (NPP) is a common clinical symptom, its pathological mechanism is complex, and there is currently no good treatment method. Therefore, exploring the treatment method of NPP is a critical issue that needs to be urgently solved. METHODS: Neural stem cells (NSC) and microencapsulated neural stem cells (MC-NSC) were transplanted into the site of sciatic nerve injury, and behavioral methods were used to detect changes in pain. Expression levels of P2X7R were detected in the dorsal root ganglion (DRG) by molecular biological methods. RESULTS: After sciatic nerve injury, mechanical withdrawal thresholds (MWT) and thermal withdrawal latency (TWL) of rats were significantly reduced, the expression levels of P2X7R in the DRG were significantly increased. After transplantation of NSC and MC-NSC, it was found that expression levels of P2X7R were significantly reduced and pain was significantly suppressed. Importantly, compared with NSC transplantation, MC-NSC could better reduce the expression levels of P2X7R and inhibit pain. CONCLUSION: MC-NSC can better decrease the expression levels of P2X7R and relieve NPP. Our results provide a novel method and data support for the treatment of NPP.

The role of P2X4 receptor in neuropathic pain and its pharmacological properties.

Neuropathic pain (NPP) is a common symptom of most diseases in clinic, which seriously affects the mental health of patients and brings certain pain to patients. Due to its pathological mechanism is very complicated, and thus, its treatment has been one of the challenges in the field of medicine. Therefore, exploring the pathogenesis and treatment approach of NPP has aroused the interest of many researchers. ATP is an important energy information substance, which participates in the signal transmission in the body. The P2 × 4 receptor (P2 × 4R) is dependent on ATP ligand-gated cationic channel receptor, which can be activated by ATP and plays an important role in the transmission of information in the nervous system and the formation of pain. In this paper, we provide a comprehensive review of the structure and function of the P2 × 4R gene. We also discuss the pathogenesis of NPP and the intrinsic relationship between P2 × 4R and NPP. Moreover, we explore the pharmacological properties of P2 × 4R antagonists or inhibitors used as targeted therapies for NPP.

The role and pharmacological characteristics of ATP-gated ionotropic receptor P2X in cancer pain.

Many factors are involved in the development of cancer pain, which is a serious complication of cancer and affects the quality of life of patients, Normally, drugs are used to relieve pain in clinic, but the effect is not satisfactory to patients. Therefore, it is necessary to explore the molecular basis of the pathogenesis of cancer pain and carry out targeted therapy. Fortunately, the important role of P2X purine receptors dependent on ATP ion channels in the development of cancer pain has been recognized. In the development of cancer, ATP concentration in the tumor microenvironment is high enough to activate P2X purine receptors, sensitive peripheral receptors, enhance sensory nerve fiber information transmission, sensitize the central nervous system, and induce or aggravate pain. Here, we outlined the role of P2X purine receptors in the development of cancer, and discussed the intrinsic correlation between P2X purine receptors and cancer pain. Moreover, we also explored the pharmacological properties of P2X antagonists or inhibitors to inhibit cancer pain, and hope to provide some value for the treatment of cancer pain in the future. In short, up-regulation of P2X expression can induce or aggravate cancer pain, while reducing P2X expression level can inhibit cancer pain. Therefore, P2X may be another potential pharmacological target for the treatment of cancer pain.

Association between the rs3751143 polymorphism of P2RX7 gene and chronic lymphocytic leukemia: A meta-analysis.

OBJECTIVES: Meta-analysis was used to determine the association between rs3751143 polymorphism of P2RX7 gene and the risk of chronic lymphocytic leukemia (CLL). METHODS: Search for published articles about the association between the rs3751143 and CLL in PubMed, MEDINE, Web of Science, and Embase databases, with a calculated odds ratio of (OR) and 95% confidence interval (95%CI). RESULTS: A total of 1184 cases and 1725 controls in 8 studies were pooled together for evaluation of the overall association between rs3751143 and risk of CLL. Allele model (A vs C, p = 0.16, OR = 0.85, 95%CI = 0.71-1.17), homozygous model (AA vs CC, p = 0.07; OR = 0.78, 95%CI = 0.84-1.08), and heterozygous model (AC vs CC, p = 0.76; OR = 0.85; 95%CI = 0.68-0.79) did not show decreased risk of developing CLL. Similarly, dominant model (AA + AC vs. CC: p = 0.58; OR = 1.10, 95%CI = 0.69-1.75), and recessive model (AA vs AC + CC, p = 0.21, OR = 1.18, 95%CI = 0.70-1.99) failed to show decreased risk of developing CLL. However, in familial, heterozygous model (AC vs. CC: p = 0.0006, OR = 0.64, 95%CI = 0.67-1.50) and recessive model (AA vs. AC + CC: p = 0.0017; OR = 1.02, 95%CI = 0.73-2.35) indicated the association between the inheritance of rs3751143 and the risk of developing CLL. In the overall survival prognosis, no significant association between rs3751143 and CLL was detected with relatively high heterogeneity. CONCLUSIONS: Our pooled data indicates that there is a correlation between the inheritance of rs3751143 and the risk of CLL in familial.

Genome Sequence Analysis of Clostridium tyrobutyricum, a Promising Microbial Host for Human Health and Industrial Applications.

Clostridium tyrobutyricum is a promising microbial host for the anaerobic production of bio-based chemicals, especially butyric acid. At the same time, it also has great potential as a probiotic for the production of short-chain fatty acids in the intestines. However, due to the insufficient knowledge of the genetic characteristics of this organism, there has been little progress in its genetic engineering to date. Here, we present the complete genome sequence of C. tyrobutyricum L319, which consists of a circular chromosome and a plasmid with a G + C content of 31.69%, encompassing approximately 3.09 Mb with 3052 protein-coding genes. Functional gene annotation revealed better results than previous studies based on KEGG pathway classification. Furthermore, we obtained detailed functional characterization of 93 genes previously annotated as putative proteins. Genomic analysis revealed that this organism contains multiple genes encoding enzymes involved in the CRISPR-Cas systems, substrate utilization, isopeptide and ester bonds, transcriptional regulation, and oxidative stress. The safety evaluation at genetic level indicated that this organism does not possess transferable resistance genes, invasive defensive pathogenicity factors, or harmful enzymes. The genome sequence data analyzed in this study will be available for further research and will facilitate the further understanding and development of potential applications of C. tyrobutyricum.

DJ-1 is involved in the multidrug resistance of SGC7901 gastric cancer cells through PTEN/PI3K/Akt/Nrf2 pathway.

Gastric cancer is a common malignancy worldwide. The occurrence of multidrug resistance (MDR) is the major obstacle for effective gastric cancer chemotherapy. In this study, the in-depth molecular mechanism of the DJ-1-induced MDR in SGC7901 gastric cancer cells was investigated. The results showed that DJ-1 expression level was higher in MDR variant SGC7901/VCR cells than that in its parental SGC7901 cells. Moreover, DJ-1 overexpression conferred the MDR phenotype to SGC7901 cells, while DJ-1 knockdown in SGC7901/VCR cells induced re-sensitization to adriamycin, vincristine, cisplatin, and 5-fluorouracil. These results suggested that DJ-1 mediated the development of MDR in SGC7901 gastric cancer cells. Importantly, further data revealed that the activation of PI3k/Akt and Nrf2 signaling pathway were required for the DJ-1-induced MDR phenotype in SGC7901 gastric cancer cells. Meanwhile, we found that PI3k/Akt pathway was activated probably through DJ-1 directly binding to and negatively regulating PTEN, consequently resulting in Nrf2 phosphorylation and activation, and thereby inducing Nrf2-dependent P-glycoprotein (P-gp) and Bcl-2 expressions in the DJ-1-mediated MDR of SGC7901 gastric cancer cells. Overall, these results revealed that activating PTEN/PI3K/Akt/Nrf2 pathway and subsequently upregulating P-gp and Bcl-2 expression could be a critical mechanism by which DJ-1 mediates the development of MDR in SGC7901 gastric cancer cells. The new findings may be helpful for understanding the mechanisms of MDR in gastric cancer cells, prompting its further investigation as a molecular target to overcome MDR.

Transplantation of microencapsulated olfactory ensheathing cells inhibits the P2X2 receptor over-expressionmediated neuropathic pain in the L4-5 spinal cord segment.

OBJECTIVES: The purpose of this study was to determine the effect of microencapsulated olfactory ensheathing cells (MC-OECs) transplantation on neuropathic pain (NPP) caused by sciatic nerve injury in rats, and its relationship with the expression levels of P2X2 receptor (P2X2R) in the L4-5 spinal cord segment. METHODS: Olfactory bulb tissue was removed from a healthy Sprague-Dawley (SD) rat for culturing olfactory ensheathing cells (OECs). Forty-eight SD rats were randomly divided into four groups (12 per group): the sham, chronic constriction injury (CCI), olfactory ensheathing cells (OECs), and MC-OECs groups. On days 7 and 14 after surgery, the mechanical withdrawal thresholds (MWT) were measured by using behavioral method. The expression levels of P2X2R in the L4-5 spinal cord segment were detected by in situ hybridization and Western blotting. RESULTS: On days 7 and 14 post-surgical, the MWT of rats from high to low were the sham, MC-OECs, OECs, and CCI groups, the MWT of rats in the MC-OECs groups were higher than that in OECs groups. The expression levels of P2X2R in the L4-5 spinal cord segment from high to low were the CCI, OECs, MC-OECs, and sham groups, the expression levels of P2X2R were lower than that in OECs groups. All differences between groups were statistically significant (p value <.05). CONCLUSIONS: OECs and MC-OECs transplantation can reduce the expression levels of P2X2R genes in the L4-5 spinal cord segment, and relieve NPP. The therapeutic efficacy of MC-OECs transplantation was better than the transplantation of OECs.

Prognostic significance of peripheral blood-derived neutrophil/lymphocyte ratio in patients with digestive cancer.

Accumulating studies reported the clinical value of derived neutrophil/lymphocyte ratio (dNLR) regarding the prediction of survival outcomes in digestive cancers, however, the prognostic significances of dNLR in these cancers were inconsistent. This study was carried out to clarify the relationship between circulating dNLR and prognosis in gastrointestinal (GI) cancers. Eligible publications were collected and extracted by searching Pubmed, Embase, Web of Science, and Google Scholar up to November 21, 2018. The prognostic impact of dNLR in subjects with GI cancers was assessed with the overall hazard ratios (HRs). A total of 26 studies with up to 13,945 participants were recruited. Our findings showed that peripheral blood dNLR before treatment could be a useful prognostic predictor in digestive cancers, an elevated dNLR indicated a shorter overall survival (OS) in GI tumors (HR, 1.44; 95% confidence interval [CI], 1.36-1.51). Furthermore, its significant prognostic value for OS was also confirmed in subgroup analyses stratified by disease type, publication year, type of research, detection method, geographic location, cut-off value, treatment, analysis type, follow-up time and disease stage. In addition, high dNLR was significantly associated with worse cancer-specific survival (HR, 1.25; 95% CI, 1.04-1.47) and inferior event-free survival (HR, 1.22; 95% CI, 1.11-1.33) in patients with digestive cancers. Our study showed elevated peripheral blood dNLR may indicate unfavorable outcomes in digestive cancer.

DJ-1 overexpression confers the multidrug resistance phenotype to SGC7901 cells by upregulating P-gp and Bcl-2.

Gastric cancer (GC) is one of the most malignant tumors with high incidence and mortality worldwide, and the multidrug resistance (MDR) often results in chemotherapy failure in GC. DJ-1 has been well indicated to be associated with drug resistance in multiple cancers. However, the role of DJ-1 in the MDR of gastric cancer cells and its possible mechanism remain to be elucidated. Therefore, the current study was investigated whether DJ-1 expression is differential in parental gastric cancer cell SGC7901 and vincristine (VCR)-induced gastric cancer MDR cell SGC7901/VCR, and whether DJ-1 plays a significant role in development of MDR in gastric cancer. The results showed that DJ-1 expression in SGC7901/VCR cells was significantly higher than its sensitive parental SGC7901 cells. Furthermore, DJ-1 overexpressed gastric cancer cell line SGC7901/LV-DJ-1 led to the increase of cell survival rate, the IC50 of chemotherapeutic drugs and number of cell clones as well as decrease of cell cycle G0/G1 phase ratio compared with its parental cells under the treatment of VCR, adriamycin (ADR), 5-Fluorouracil (5-FU) and cisplatin (DDP). However, the DJ-1 knockdown stable cell line SGC7901/VCR/shDJ-1 reversed the above mentioned series of MDR. Moreover, it was found that upregulation of DJ-1 protein expression promoted the pumping rate of GC cells to ADR and reduced the apoptotic index of GC cells treated with chemotherapeutic drugs by upregulating P-gp and Bcl-2. Similarly, knocking down DJ-1, P-gp or Bcl-2 displayed a converse effect. In conclusion, the current study demonstrated that DJ-1 overexpression confers the MDR phenotype to SGC7901 cells and this process is related to DJ-1 promoting active efflux of drugs and enhancing the anti-apoptotic ability of MDR GC cells by upregulating P-gp and Bcl-2.

Enhanced acid-stress tolerance in Lactococcus lactis NZ9000 by overexpression of ABC transporters.

BACKGROUND: Microbial cell factories are widely used in the production of acidic products such as organic acids and amino acids. However, the metabolic activity of microbial cells and their production efficiency are severely inhibited with the accumulation of intracellular acidic metabolites. Therefore, it remains a key issue to enhance the acid tolerance of microbial cells. In this study, we investigated the effects of four ATP-binding cassette (ABC) transporters on acid stress tolerance in Lactococcus lactis. RESULTS: Overexpressing the rbsA, rbsB, msmK, and dppA genes exhibited 5.8-, 12.2-, 213.7-, and 5.2-fold higher survival rates than the control strain, respectively, after acid shock for 3 h at pH 4.0. Subsequently, transcriptional profile alterations in recombinant strains were analyzed during acid stress. The differentially expressed genes associated with cold-shock proteins (csp), fatty acid biosynthesis (fabH), and coenzyme A biosynthesis (coaD) were up-regulated in the four recombinant strains during acid stress. Additionally, some genes were differentially expressed in specific recombinant strains. For example, in L. lactis (RbsB), genes involved in the pyrimidine biosynthetic pathway (pyrCBDEK) and glycine or betaine transport process (busAA and busAB) were up-regulated during acid stress, and the argG genes showed up-regulations in L. lactis (MsmK). Finally, we found that overexpression of the ABC transporters RbsB and MsmK increased intracellular ATP concentrations to protect cells against acidic damage in the initial stage of acid stress. Furthermore, L. lactis (MsmK) consistently maintained elevated ATP concentrations under acid stress. CONCLUSIONS: This study elucidates the common and specific mechanisms underlying improved acid tolerance by manipulating ABC transporters and provides a further understanding of the role of ABC transporters in acid-stress tolerance.

Stress tolerance phenotype of industrial yeast: industrial cases, cellular changes, and improvement strategies.

Yeast is widely used in the baking, biocontrol, brewing, and bio manufacturing industries. In the baking industry alone, around two million tons of yeast are consumed worldwide every year. While yeast brings delicious and healthy lives to humans, we find that stress resistance of yeast is essential for the development of bioindustry. Whether during baking, biocontrol, brewing, bio manufacturing, or in other industries, yeast faces a variety of environmental stresses that have a great impact on its activity, transformation ability, etc., which make the production process uncertain. Therefore, robust yeast strains that can resist various environmental and endogenous stresses are needed. In recent years, many studies have investigated the stress resistance of laboratory strains and specific methods to improve stress resistance; however, applying these findings to industrial yeast is difficult. In this paper, based on summarizing the work of predecessors, we put forward the main steps to improve the stress resistance of industrial yeast systematically, which may provide a reference for researchers.