Nano-energy interference: A novel strategy for blunting tumor adaptation and metastasis.

Blunting the tumor's stress-sensing ability is an effective strategy for controlling tumor adaptive survival and metastasis. Here, we have designed a cyclically amplified nano-energy interference device based on lipid nanoparticles (LNP), focused on altering cellular energy metabolism. This innovative nano device efficiently targets and monitors the tumor's status while simultaneously inhibiting mitochondrial respiration, biogenesis and ribosome production. To this end, we first identified azelaic acid (AA), a binary acid capable of disrupting the mitochondrial respiratory chain. Upon encapsulation in LNP and linkage to mitochondrial-targeting molecules, this disruptive effect is further augmented. Consequently, tumors exhibit a substantial upregulation of the glycolytic pathway, intensifying their glucose demand and worsening the tumor's energy-deprived microenvironment. Then, the glucose analog, 2-Deoxy-D-glucose (2-DG), linked to the LNP, efficiently targets tumors and competitively inhibits the tumor's normal glucose uptake. The synergetic results of combining AA with 2-DG induce comprehensive energy deficiency within tumors, blocking the generation of energy-sensitive ribosomes. Ultimately, the disruption of both mitochondria and ribosomes depletes energy supply and new protein-generating capacity, weakening tumor's ability to adapt to environmental stress and thereby inhibiting growth and metastasis. Comprehensively, this nano-energy interference device, by controlling the tumor's stress-sensing ability, provides a novel therapeutic strategy for refractory tumors.

Quantitative microbiological risk assessments for Salmonella spp. contaminated taiwanese salty chicken in the taiwanese population.

The aim of the study is to develop Salmonella spp. Quantitative microbial risk assessments (QMRA) and to evaluate the risk of Salmonellosis illness in the Taiwanese population after consumption of Taiwanese salty chicken (TSC). We assume that Salmonella spp. May contaminate the fresh raw chicken used in TSC. After transport to the diner, fresh raw chicken is received, cleaned, and surface-washed by diner staff. The TSC is then cooked and sold to consumers. We set four different cross-contamination scenarios to evaluate the contamination level of Salmonella spp. In TSC. We used a Monte Carlo simulation method, a probabilistic analysis method, and exceedance risk to evaluate the risk of Salmonellosis illness. When the exceedance risk was 5 %, and taking the Taiwanese population above 19 years old as an example, the rate of contracting Salmonellosis from the consumption of TSC will be 2.94 % (2.94 million per 100 million people) if the chef does not clean their hands, knives, or cutting boards. However, if the chef washes their hands, knives, and cutting boards with cold water and soap, the illness rate of Salmonellosis from consuming TSC will be 1.93E-04 % (193 per 100 million people). Sensitivity analysis indicates that the most important risk factor in the QMRAs of TSC is the temperature of the fresh raw chicken during transportation, following which were the Salmonella spp. Residual. If the staff of the diner separates the cooking tools used for raw ingredients and those for cooked food, the illness risk of Salmonellosis will be very low.

Perioperative respiratory muscle training improves respiratory muscle strength and physical activity of patients receiving lung surgery: A meta-analysis.

BACKGROUND: The clinical role of perioperative respiratory muscle training (RMT), including inspiratory muscle training (IMT) and expiratory muscle training (EMT) in patients undergoing pulmonary surgery remains unclear up to now. AIM: To evaluate whether perioperative RMT is effective in improving postoperative outcomes such as the respiratory muscle strength and physical activity level of patients receiving lung surgery. METHODS: The PubMed, EMBASE (via OVID), Web of Science, Cochrane Library and Physiotherapy Evidence Database (PEDro) were systematically searched to obtain eligible randomized controlled trials (RCTs). Primary outcome was postoperative respiratory muscle strength expressed as the maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP). Secondary outcomes were physical activity, exercise capacity, including the 6-min walking distance and peak oxygen consumption during the cardio-pulmonary exercise test, pulmonary function and the quality of life. RESULTS: Seven studies involving 240 participants were included in this systematic review and meta-analysis. Among them, four studies focused on IMT and the other three studies focused on RMT, one of which included IMT, EMT and also combined RMT (IMT-EMT-RMT). Three studies applied the intervention postoperative, one study preoperative and the other three studies included both pre- and postoperative training. For primary outcomes, the pooled results indicated that perioperative RMT improved the postoperative MIP (mean = 8.13 cmH2O, 95%CI: 1.31 to 14.95, P = 0.02) and tended to increase MEP (mean = 13.51 cmH2O, 95%CI: -4.47 to 31.48, P = 0.14). For secondary outcomes, perioperative RMT enhanced postoperative physical activity significantly (P = 0.006) and a trend of improved postoperative pulmonary function was observed. CONCLUSION: Perioperative RMT enhanced postoperative respiratory muscle strength and physical activity level of patients receiving lung surgery. However, RCTs with large samples are needed to evaluate effects of perioperative RMT on postoperative outcomes in patients undergoing lung surgery.

Predictive value of prognostic nutritional index on infection after radical gastrectomy: a retrospective study.

Background: The prognostic nutritional index (PNI) is a useful tool to evaluate nutritional status, which is associated with postoperative complications and prognosis of patients with cancer. Recent studies have shown that PNI has important predictive value for postoperative infection in cancer patients. However, the role and clinical value of PNI in infection after radical gastrectomy remains unclear. This study investigated the relationship between PNI and infection after radical surgery for gastric cancer (GC), focusing on the predictive value of PNI. Methods: A total of 1,111 patients with primary gastric cancer who underwent radical surgery in our hospital from December 2010 to December 2020 were included in this retrospective study. The demographic and clinicopathological data of all patients were acquired through hospital information system (HIS). Preoperative serum albumin (ALB) level and peripheral blood lymphocyte count were obtained for PNI calculation. We selected 812 patients by propensity score matching to reduce biases due to the different distributions of co-variables among the comparable groups. The factors influencing postoperative infection in the matched patients were explored using univariate and multivariate analyses. Results: Baseline characteristics significantly differed among patients with different PNI scores. After one-to-one matching, the clinicopathological data of the 2 groups were comparable, and 812 patients were included for further analysis. Among these patients, 101 developed infections, with an infection rate of 12.4%, which were mainly caused by gram-negative bacteria. The incidence of infection was significantly higher in the low PNI group than in the high PNI group. Univariate and multivariate analyses identified body mass index (BMI) ≥25 kg/m2 [odds ratio (OR) =2.314, P=0.004], diabetes mellitus (OR =1.827, P=0.042), PNI score <45 (OR =2.138, P=0.037), combined multi-organ resection (OR =2.946, P<0.001), operation time ≥240 minutes (OR =2.744, P=0.023), and perioperative blood transfusion (OR =2.595, P=0.025) as risk factors for infection after radical surgery for GC. Conclusions: Infection is the most common complication after radical gastrectomy for GC, and a low preoperative PNI score is a risk factor for postoperative infection.

Downregulation of PDGF-D Inhibits Proliferation and Invasion in Breast Cancer MDA-MB-231 Cells.

BACKGROUND: The platelet derived growth factor-D (PDGF-D) plays an important role in breast tumor aggressiveness. However, limited study has investigated the effect of silencing PDGF-D on the biological function of breast cancer. The purpose of this study is to clarify the potential value of PDGF-D as a target for breast cancer treatment. METHODS: Reverse transcription-polymerase chain reaction and western blot were used to detect PDGF-D expression in 5 different breast cancer cells. The lentiviral vector was usd to silence PDGF-D in MDA-MB-231 cells. Then, Methyl Thiazolyl Tetrazolium was used to detect cell viability, 5-Ethynyl-2'- deoxyuridine and a soft agar assay were used to detect cell proliferation and clonality. Additionally, cell apoptosis after PDGF-D knockdown was measured by Annexin V/ Prodium Iodide staining, and cell migration was detected by trans-well assay. Survival rate and tumor size were measured by nude mice transplantation. RESULTS: The MDA-MB-231 and SK-BR-3 cell lines showed higher PDGF-D expression than the MCF7 cell lines (P<.05). After the PDGF-D gene was silenced, the growth and colony forming abilitys ignificantly decreased (P<.05) together with the induction of apoptosis in MDA-MB-231 cells (P<.05). Moreover, MDA-MB-231 cells with PDGF-D silencing showed significantly diminished aggressive migration and invasion potential compared to other cells (P<.05). In vivo experiments also indicated that PDGF-D silencing inhibited tumor growth and improved the survival rate of tumor-bearing mice. CONCLUSION: Downregulation of PDGF-D had dramatic effects on breast cancer cell proliferation, apoptosis and migration, which indicates that it plays an important role in breast cancer development and progression.

Microbial Risk Assessment of Escherichia coli O157:H7 in Beef Imported from the United States of America to Taiwan.

Outbreaks of foodborne illness caused by pathogenic Escherichia coli (E. coli) O157:H7, which are attributable to the consumption of undercooked beef, have occurred in many countries. In Taiwan, the production of domestic beef accounts for only 5% of the total amount of beef sold. Therefore, we applied different contextual assumptions to develop a quantitative microbial risk assessment of E. coli O157:H7 and evaluated the risk of illness in the Taiwanese population consuming beef imported from the United States of America. The probability distribution showed that, in males aged 19-65 years in the Taiwanese population, for example, when rare beef was consumed 100 servings, there was a 90% probability of randomly intaking seven colony forming units of E. coli O157:H7. When medium beef was consumed 10,000 servings, there was a 90% probability of randomly intaking two colony forming units of E. coli O157:H7. When the exceedance risk was 5%, the rate of foodborne illnesses caused by consuming rare beef contaminated with E. coli O157:H7 was 10-28 cases per 1 million individuals. For medium beef, this rate was 6-13 per 100 million individuals. Sensitivity analyses indicated that the amount of E. coli O157:H7 remaining in beef products after cooking was the most important risk factor, followed by the amount of beef products consumed. Proper cooking of imported beef consumed by the Taiwanese public reduces the incidence of foodborne disease to almost zero, without risk of harm to health.

Overexpression of gelsolin reduces the proliferation and invasion of colon carcinoma cells.

The enhanced motility of cancer cells via the remodeling of the actin cytoskeleton is crucial in the process of cancer cell invasion and metastasis. It was previously demonstrated that gelsolin (GSN) may be involved as a tumor or a metastasis suppressor, depending on the cell lines and model systems used. In the present study, the effect of GSN on the growth and invasion of human colon carcinoma (CC) cells was investigated using reverse transcription quantitative polymerase chain reaction and western blotting. It was observed that upregulation of the expression of GSN in human CC cells significantly reduced the invasiveness of these cells. The expression levels of GSN were observed to be reduced in CC cells, and the reduced expression level of GSN was often associated with a poorer metastasis­free survival rate in patients with CC (P=0.04). In addition, the overexpression of GSN inhibited the invasion of CC cells in vitro. Furthermore, GSN was observed to inhibit signal transducer and activator of transcription (STAT) 3 signaling in CC cells. Together, these results suggested that GSN is critical in regulating cytoskeletal events and inhibits the invasive and/or metastatic potential of CC cells. The results obtained in the present study may improve understanding of the functional and mechanistic links between GSN as a possible tumor suppressor and the STAT3 signaling pathway, with respect to the aggressive nature of CC. In addition, the present study demonstrated the importance of GSN in regulating the invasion and metastasis of CC cells at the molecular level, suggesting that GSN may be a potential predictor of prognosis and treatment success in CC.