Regeneration of Non-Alcoholic Fatty Liver Cells Using Chimeric FGF21/HGFR: A Novel Therapeutic Approach.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant liver ailment attributed to factors like obesity and diabetes. While ongoing research explores treatments for NAFLD, further investigation is imperative to address this escalating health concern. NAFLD manifests as hepatic steatosis, precipitating insulin resistance and metabolic syndrome. This study aims to validate the regenerative potential of chimeric fibroblast growth factor 21 (FGF21) and Hepatocyte Growth Factor Receptor (HGFR) in NAFLD-afflicted liver cells. AML12, a murine hepatocyte cell line, was utilized to gauge the regenerative effects of chimeric FGF21/HGFR expression. Polysaccharide accumulation was affirmed through Periodic acid-Schiff (PAS) staining, while LDL uptake was microscopically observed with labeled LDL. The expression of FGF21/HGFR and NAFLD markers was analyzed by mRNA analysis with RT-PCR, which showed a decreased expression in acetyl-CoA carboxylase 1 (ACC1) and sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) with increased expression of hepatocellular growth factor (HGF), hepatocellular nuclear factor 4 alpha (HNF4A), and albumin (ALB). These findings affirm the hepato-regenerative properties of chimeric FGF21/HGFR within AML12 cells, opening novel avenues for therapeutic exploration in NAFLD.

Amorphous-Crystalline Interfaces on Hollow Nanocubes Derived from Ir-Doped Ni-Fe-Zn Prussian Blue Analog Enables High Capability of Alkaline/Acidic/Saline Water Oxidations.

Development of highly efficient and robust electrocatalysts for oxygen evolution reaction (OER) under specific electrolyte is a key to actualize commercial low-temperature water electrolyzers. Herein, a rational catalyst design strategy is first reported based on amorphous-crystalline (a-c) interfacial engineering to achieve high catalytic activity and durability under diverse electrolytes that can be used for all types of low-temperature water electrolysis. Abundant a-c interface (ACI) is implemented into a hollow nanocubic (pre)-electrocatalyst which is derived from Ir-doped Ni-Fe-Zn Prussian blue analogues (PBA). The implemented c-a interface is well maintained during prolonged OER in alkaline, alkalized saline, and acidic electrolytes demonstrating its diverse functionality for water electrolysis. Notably, the final catalyst exhibits superior catalytic activity with excellent durability for OER compared to that of benchmark IrO2 catalyst, regardless of chemical environment of electrolytes. Hence, this work can be an instructive guidance for developing the ACI engineered electroctalyst which can be diversely used for different types of low-temperature electrolyzers.

Effect of IL-10-producing B cells in peripheral blood and tumor tissue on gastric cancer.

BACKGROUND: Interleukin (IL)-10-producing B (B10) cells are generated in response to signals from the tumor microenvironment and promote tumor growth by interacting with B10 cells. We investigated the distributions of immune cells in peripheral blood and tumor tissue samples from patients with gastric cancer (GC). METHODS: Patients with GC who underwent radical gastrectomy in Seoul St. Mary's Hospital between August 2020 and May 2021 were enrolled in this study. Forty-two samples of peripheral blood were collected, and a pair of gastric mucosal samples (normal and cancerous mucosa; did not influence tumor diagnosis or staging) was collected from each patient after surgery. B10 cells in peripheral blood and cancer mucosa samples were investigated by flow cytometry and immunofluorescence. AGS cells, gastric cancer cell line, were cultured with IL-10 and measured cell death and cytokine secretion. Also, AGS cells were co-cultured with CD19 + B cells and measured cytokine secretion. RESULTS: The population of B10 cells was significantly larger in the blood of patients with GC compared with controls. In confocal images of gastric mucosal tissues, cancerous mucosa contained more B10 cells than normal mucosa. The population of B10 cells in cancerous mucosa increased with cancer stage. When AGS cells were cultured under cell-death conditions, cellular necrosis was significantly decreased, and proliferation was increased, for 1 day after IL-10 stimulation. Tumor necrosis factor (TNF)-α, IL-8, IL-1ß, and vascular endothelial growth factor secretion by cancer cells was significantly increased by coculture of AGS cells with GC-derived CD19+ B cells. CONCLUSIONS: B cells may be one of the populations that promote carcinogenesis by inducing the production of inflammatory mediators, such as IL-10, in GC. Targeting B10 cells activity could improve the outcomes of antitumor immunotherapy. Video Abstract.

Impact of postoperative NSAIDs (IV-PCA) use on short-term outcomes after laparoscopic gastrectomy for the patients of gastric cancer.

BACKGROUND: Further data are necessary to evaluate the risk of complications associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs) postoperatively. This study aimed to determine the correlation between the use of NSAIDs in intravenous patient-controlled analgesia (IV-PCA) and postoperative complications after laparoscopic gastrectomy in patients with gastric cancer. METHODS: This retrospective, single-center study was conducted. The study population comprised 2150 patients who underwent laparoscopic gastrectomy for gastric cancer treatment. They were divided into two groups: non-NSAIDs (n = 1215) and NSAIDs (n = 935) according to their use of the drugs. Clinicopathologic characteristics, operative details, postoperative complications within 30 days, risk factors for complications, and survival were analyzed. RESULTS: Of the 2150 patients, 935 (43.49%) used NSAIDs. The overall complication rate showed no significant difference between the NSAIDs and non-NSAIDs groups (22.7% vs. 20.7%, p = 0.280), while the rates of anastomotic leakage and duodenal leakage were higher in the NSAID group (2.4% vs. 0.7%, p = 0.002 and 1.8% vs. 0.6%, p = 0.007, respectively). The rates of intra-abdominal bleeding and intra-abdominal abscess were significantly higher in the NSAID group (2.1% vs. 0.7%, p = 0.005 and 1.5% vs. 0.4%, p = 0.008, respectively). However, postoperative ileus occurred more frequently in the non-NSAID group (3.0% vs. 1.4%, p = 0.015). On multivariate analysis, NSAID use was an independent risk factor for early postoperative complications (1.303 [1.042-1.629], p = 0.020). Meanwhile, the NSAID group showed no differences in overall survival at each pathological stage. CONCLUSION: Postoperative NSAID use by IV-PCA is associated with anastomotic leakage, duodenal stump leakage, intra-abdominal bleeding, and intra-abdominal abscess in patients who underwent laparoscopic gastrectomy for gastric cancer. Caution is advised when NSAIDs are used peri-operatively.

Design and synthesis of endocannabinoid enzyme inhibitors for ocular indications.

A small library of FAAH and dual FAAH/MAGL inhibitors designed for peripheral selectivity were targeted. Of these compounds, three were identified to have desirable FAAH inhibition and reduced permeability in a PAMPA assay. Those three compounds were advanced into a MAGL inhibitor assay and one was found to be a relative selective FAAH inhibitor, FAAH to MAGL IC50 ratio of 1:27, and one was found to be more characteristic of a true dual enzyme inhibitor, FAAH to MAGL IC50 ratio of 1:4. Both compounds showed activity in an ABPP assay, blockage of TAMRA-FP labeling of FAAH and MAGL in rat eye homogenate.

The First Systematic Gastroscopy Training Program for Surgeons in Korea.

BACKGROUND: Endoscopic evaluation of the stomach is essential for preoperative planning and post-surgical surveillance for various diseases of the stomach, including malignancy. The gastroscopy education program for surgeons is currently in its infancy and is not systematically organized in Korea. This study aimed to introduce the first systematic gastroscopy education program for surgeons in Korea. METHODS: The gastroscopy education program entitled "Gastroscopy School for Surgeons (GSS)" comprised of theoretical education, dry lab hands-on training, and clinical practice. All participants were beginners without any gastroscopy experience. Clinical practice started after the completion of the theoretical and dry lab training. The gastroscopy practices utilized simple luminal observation, biopsy, localization using clips or dye injection, and limited therapeutic gastroscopy. The educational performances and surveys from 33 participants were analyzed. RESULTS: The participants consisted of surgical residents, general surgeons, gastrointestinal-specialized surgeons, and physicians. Participants performed a total of 2,272 gastroscopies, 2,008 of which were post-gastrectomy cases. Currently, of the 33 participants, 7 (21.2%) of the participants performed gastroscopy regularly, and 7 (21.2%) occasionally. According to the self-reported survey, one participant assessed their current gastroscopic technique to be at the expert level, and 25 (75.8%) at a proficient level. All participants considered gastroscopy education for surgeons to be necessary, and 28 (84.8%) stated that systematic education is not currently provided in Korea. CONCLUSION: We introduced the first systematic gastroscopy education program for surgeons in Korea, namely the GSS, which is practical and meets clinical needs. More training centers are needed to expand gastroscopy training among Korean surgeons.

Intranasal Administration of Codium fragile Polysaccharide Elicits Anti-Cancer Immunity against Lewis Lung Carcinoma.

Natural polysaccharides have shown promising effects on the regulation of immunity in animals. In this study, we examined the immune stimulatory effect of intranasally administered Codium fragile polysaccharides (CFPs) in mice. Intranasal administration of CFPs in C57BL/6 mice induced the upregulation of surface activation marker expression in macrophages and dendritic cells (DCs) in the mediastinal lymph node (mLN) and the production of interleukin-6 (IL-6), IL-12p70, and tumor necrosis factor-α in bronchoalveolar lavage fluid. Moreover, the number of conventional DCs (cDCs) was increased in the mLNs by the upregulation of C-C motif chemokine receptor 7 expression, and subsets of cDCs were also activated following the intranasal administration of CFP. In addition, the intranasal administration of CFPs promoted the activation of natural killer (NK) and T cells in the mLNs, which produce pro-inflammatory cytokines and cytotoxic mediators. Finally, daily administration of CFPs inhibited the infiltration of Lewis lung carcinoma cells into the lungs, and the preventive effect of CFPs on tumor growth required NK and CD8 T cells. Furthermore, CFPs combined with anti-programmed cell death-ligand 1 (PD-L1) antibody (Ab) improved the therapeutic effect of anti-PD-L1 Ab against lung cancer. Therefore, these data demonstrated that the intranasal administration of CFP induced mucosal immunity against lung cancer.

Unveiling 79-Year-Old Ixene and Its BN-Doped Derivative.

Polycyclic aromatic hydrocarbons (PAHs) are key components of organic electronics. The electronic properties of these carbon-rich materials can be controlled through doping with heteroatoms such as B and N, however, few convenient syntheses of BN-doped PAHs have been reported. Described herein is the rationally designed, two-step syntheses of previously unknown ixene and BN-doped ixene (B2 N2 -ixene), and their characterizations. Compared to ixene, B2 N2 -ixene absorbs longer-wavelength light and has a smaller electrochemical energy gap. In addition to its single-crystal structure, scanning tunneling microscopy revealed that B2 N2 -ixene adopts a nonplanar geometry on a Au(111) surface. The experimentally obtained electronic structure of B2 N2 -ixene and the effect of BN-doping were confirmed by DFT calculations. This synthesis enables the efficient and convenient construction of BN-doped systems with extended π-conjugation that can be used in versatile organic electronics applications.

Functional expression of dopamine D2 receptor is regulated by tetraspanin 7-mediated postendocytic trafficking.

The dopaminergic system plays an essential role in various functions of the brain, including locomotion, memory, and reward, and the deregulation of dopaminergic signaling as a result of altered functionality of dopamine D2 receptor (DRD2) is implicated in multiple neurologic and psychiatric disorders. Tetraspanin-7 (TSPAN7) is expressed to variable degrees in different tissues, with the highest level in the brain, and multiple mutations in TSPAN7 have been implicated in intellectual disability. Here, we tested the hypothesis that TSPAN7 may be a binding partner of DRD2 that is involved in the regulation of its functional activity. Our results showed that TSPAN7 was associated with DRD2 and reduced its surface expression by enhancing DRD2 internalization. Immunocytochemical analysis revealed that TSPAN7 that resides in the plasma membrane and early and late endosomes promoted internalization of DRD2 and its localization to endosomal compartments of the endocytic pathway. Furthermore, we observed that TSPAN7 deficiency increased surface localization of DRD2 concurrent with the decrease of its endocytosis, regardless of dopamine treatment. Finally, TSPAN7 negatively affects DRD2-mediated signaling. These results disclosed a previously uncharacterized role of TSPAN7 in the regulation of the expression and functional activity of DRD2 by postendocytic trafficking.-Lee, S.-A., Suh, Y., Lee, S., Jeong, J., Kim, S. J., Kim, S. J., Park, S. K. Functional expression of dopamine D2 receptor is regulated by tetraspanin 7-mediated postendocytic trafficking.

Risk of Malignancy in Thyroid Incidentaloma is Not Increased in Overweight or Obese Patients, but in Young Patients.

Thyroid incidentaloma is defined as an unsuspected, asymptomatic thyroid lesion that is discovered on an imaging study or during an operation unrelated to the thyroid gland. We aim to evaluate the relationship between overweight or obese and risk of malignancy in patients with thyroid incidentaloma detected by F18-flurodeoxyglucose positron emission tomography/computed tomography and factors to predict risk of malignancy in thyroid incidentaloma. From January 2010 to December 2013, a total of 238 patients were eligible for this study. Using the Bethesda system for reporting thyroid cytopathology, categories I-III were defined as a nonmalignancy and categories V-VI were defined as a malignancy. When patients with body mass index (BMI) of less than 23 and 23 or more were divided into two groups of normal and overweight or obese, risk of malignancy of thyroid incidentaloma was not significantly different between two groups (P = 0.1812). In logistic regression analysis, age was the only variable that showed a significant association with malignancy of thyroid incidentaloma (odds ratio 0.9608, P = 0.0021). However, none of sex, height, weight, and BMI was predictor of malignancy of thyroid incidentaloma. We demonstrated that being overweight or obese did not increase rate of malignancy in patients with thyroid incidentaloma.

Comparison of Visual Assessment of Breast Density in BI-RADS 4th and 5th Editions With Automated Volumetric Measurement.

OBJECTIVE: The purpose of this study was to compare visual assessments of mammographic breast density by radiologists using BI-RADS 4th and 5th editions in correlation with automated volumetric breast density measurements. MATERIALS AND METHODS: A total of 337 consecutive full-field digital mammographic examinations with standard views were retrospectively assessed by two radiologists for mammographic breast density according to BI-RADS 4th and 5th editions. Fully automated measurement of the volume of fibroglandular tissue and total breast and percentage breast density was performed with a commercially available software program. Interobserver and intraobserver agreement was assessed with kappa statistics. The distributions of breast density categories for both editions of BI-RADS were compared and correlated with volumetric data. RESULTS: Interobserver agreement on breast density category was moderate to substantial (κ = 0.58-0.63) with use of BI-RADS 4th edition and substantial (κ = 0.63-0.66) with use of the 5th edition but without significant difference between the two editions. For intraobserver agreement between the two editions, the distributions of density category were significantly different (p < 0.0001), the proportions of dense breast increased, and the proportion of fatty breast decreased with use of the 5th edition compared with the 4th edition (p < 0.0001). All volumetric breast density data, including percentage breast density, were significantly different among density categories (p < 0.0001) and had significant correlation with visual assessment for both editions of BI-RADS (p < 0.01). CONCLUSION: Assessment using BI-RADS 5th edition revealed a higher proportion of dense breast than assessment using BI-RADS 4th edition. Nevertheless, automated volumetric density assessment had good correlation with visual assessment for both editions of BI-RADS.

COX-2- and endoplasmic reticulum stress-independent induction of ULBP-1 and enhancement of sensitivity to NK cell-mediated cytotoxicity by celecoxib in colon cancer cells.

In the present study, we investigated whether celecoxib could induce the expression of NKG2D ligands in clonogenic colon cancer cells, and increase their susceptibility to NK cell-mediated cell death. Celecoxib and its non-coxib analog, 2,5-dimethyl celecoxib, induced ULBP-1 and DR5 in both COX-2 negative HCT-15 cells and COX-2 positive HT-29 cells. Celecoxib increased their susceptibility to NK92 cells in both DELFIA assay and soft agar colony forming assay. The inducibility of ULBP-1 and DR5 by celecoxib was not different between CD44- and CD44+ HCT-15 cells, and CD133- and CD133+ HT-29 cells. Celecoxib increased the susceptibility of highly clonogenic CD44+ HCT-15 and CD133+ HT-29 cells to NK92 cells, at least comparable to less clonogenic CD44- HCT-15 and CD133- HT-29 cells, respectively. In addition, celecoxib induced CHOP, and thapsigargin, an inducer of ER (endoplasmic reticulum) stress, induced DR5 but not ULBP1 in HCT-15. Taken together, these findings suggest that celecoxib induces the expression of ULBP-1 as well as DR5 in clonogenic colon cancer cells via COX-2 and ER stress-independent pathways, and increases their susceptibility to NK cells.

A cooperative activation loop among SWI/SNF, gamma-H2AX and H3 acetylation for DNA double-strand break repair.

Although recent studies highlight the importance of histone modifications and ATP-dependent chromatin remodelling in DNA double-strand break (DSB) repair, how these mechanisms cooperate has remained largely unexplored. Here, we show that the SWI/SNF chromatin remodelling complex, earlier known to facilitate the phosphorylation of histone H2AX at Ser-139 (S139ph) after DNA damage, binds to gamma-H2AX (the phosphorylated form of H2AX)-containing nucleosomes in S139ph-dependent manner. Unexpectedly, BRG1, the catalytic subunit of SWI/SNF, binds to gamma-H2AX nucleosomes by interacting with acetylated H3, not with S139ph itself, through its bromodomain. Blocking the BRG1 interaction with gamma-H2AX nucleosomes either by deletion or overexpression of the BRG1 bromodomain leads to defect of S139ph and DSB repair. H3 acetylation is required for the binding of BRG1 to gamma-H2AX nucleosomes. S139ph stimulates the H3 acetylation on gamma-H2AX nucleosomes, and the histone acetyltransferase Gcn5 is responsible for this novel crosstalk. The H3 acetylation on gamma-H2AX nucleosomes is induced by DNA damage. These results collectively suggest that SWI/SNF, gamma-H2AX and H3 acetylation cooperatively act in a feedback activation loop to facilitate DSB repair.

Combination of cancer immunotherapy with clinically available drugs that can block immunosuppressive cells.

Although cancer immunotherapy, which is able to target specifically cancer cells without detrimental effects to normal cell functions, would serve as an ideal therapeutic modality, most of the randomized clinical trials of cancer immunotherapy have not demonstrated a meaningful survival benefit to cancer patients over preexisting therapeutic modalities. Due to the discrepancy between the impressive preclinical results and the limited clinical results, the cancer immunotherapy is not accepted generally as a standard therapy for cancers. A variety of immune escape mechanisms are thought to be involved in this ineffectiveness of cancer immunotherapy. Therefore, elimination of immunosuppressive activities in tumor microenvironment will enhance the effectiveness of cancer immunotherapy, which is currently focused on activation of tumor-specific immune responses. Since there are now increasing evidences showing that many cytotoxic anticancer drugs including targeted agents given in lower-than-therapeutic doses have not only the ability to eliminate tumor cells but can also block the immunosuppressive activities in tumor microenvironments and consequently favor the development of anticancer immune responses, clinically available drugs can be considered for their rapid application to cancer immunotherapies to enhance the efficacy of cancer immunotherapies with marginal effects on cancer treatment.

Altered lipid metabolism as a predisposing factor for liver metastasis in MASLD.

Recently, the incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing due to the high prevalence of metabolic conditions, such as obesity and type 2 diabetes mellitus. Steatotic liver is a hotspot for cancer metastasis in MASLD. Altered lipid metabolism, a hallmark of MASLD, remodels the tissue microenvironment, making it conducive to the growth of metastatic liver cancer. Tumors exacerbate the dysregulation of hepatic metabolism by releasing extracellular vesicles and particles into the liver. Altered lipid metabolism influences the proliferation, differentiation, and functions of immune cells, contributing to the formation of an immunosuppressive and metastasis-prone liver microenvironment in MASLD. This review discusses the mechanisms by which the steatotic liver promotes liver metastasis progression, focusing on its role in fostering an immunosuppressive microenvironment in MASLD. Furthermore, this review highlights lipid metabolism manipulation strategies for the therapeutic management of metastatic liver cancer.

Predictors of positive tuberculin skin test in neonates exposed to pulmonary tuberculosis.

BACKGROUND: Neonates are at risk of nosocomial tuberculosis (TB) infection from health care workers (HCWs) in neonatal care facilities, which can progress to severe TB diseases. Tuberculin skin test (TST) is commonly used for TB diagnosis, but its accuracy in neonates is influenced by various factors, including bacilli Calmette-Guérin (BCG) vaccination. This study aimed to identify predictors of positive TSTs in neonates exposed to HCWs with pulmonary TB. METHODS: A retrospective observational study was conducted to compare the frequency of predictors between TST-positive and TST-negative neonates. Demographic, epidemiological, and clinical data of neonates exposed to TB, along with that of HCW and household contacts, were collected retrospectively through contact investigations with the Korean National TB Surveillance System (KNTSS) database. TSTs using 2 tuberculin units of purified protein derivative RT23 were performed on exposed neonates at the end of preventive TB treatment. Firth logistic regression was performed to identify predictors of TST positivity. RESULTS: Contact investigations revealed that 152 neonates and 54 HCWs were exposed to infectious TB index cases in 3 neonatal care facilities. Of 152 exposed neonates, 8 (5.3%) had positive TST results. Age of 6 days or more at the initial exposure is a statistically significant predictor of positive TST (Firth coefficient 2.1, 95% confidence interval 0.3-3.9, P = 0.024); BCG vaccination showed no statistical significance in both univariable and multivariable analysis. Sex, prematurity, exposure duration, duration from initial exposure to contact investigation, and isoniazid preventive treatment duration were not significant predictors. CONCLUSION: Age at the initial exposure is a significant predictor of positive TST in neonates exposed to active pulmonary TB. Given the complexities of TST interpretation, including false positives due to BCG vaccination, careful risk assessment is necessary for appropriate decision-making and resource allocation in the management of neonatal TB exposure.

Multimodal Golden DNA Superstructures (GDSs) for Highly Efficient Photothermal Immunotherapy.

DNA-templated metallization has emerged as an efficient strategy for creating nanoscale-metal DNA hybrid structures with a desirable conformation and function. Despite the potential of DNA-metal hybrids, their use as combinatory therapeutic agents has rarely been examined. Herein, we present a simple approach for fabricating a multipurpose DNA superstructure that serves as an efficient photoimmunotherapy agent. Specifically, we adsorb and locally concentrate Au ions onto DNA superstructures through induced local reduction, resulting in the formation of Au nanoclusters. The mechanical and optical properties of these metallic nanoclusters can be rationally controlled by their conformations and metal ions. The resulting golden DNA superstructures (GDSs) exhibit significant photothermal effects that induce cancer cell apoptosis. When sequence-specific immunostimulatory effects of DNA are combined, GDSs provide a synergistic effect to eradicate cancer and inhibit metastasis, demonstrating potential as a combinatory therapeutic agent for tumor treatment. Altogether, the DNA superstructure-templated metal casting system offers promising materials for future biomedical applications.

Gut microbiome-derived butyrate inhibits the immunosuppressive factors PD-L1 and IL-10 in tumor-associated macrophages in gastric cancer.

Early detection and surgical treatment are essential to achieve a good outcome in gastric cancer (GC). Stage IV and recurrent GC have a poor prognosis. Therefore, new treatments for GC are needed. We investigated the intestinal microbiome of GC patients and attempted to reverse the immunosuppression of the immune and cancer cells of GC patients through the modulation of microbiome metabolites. We evaluated the levels of programmed death-ligand 1 (PD-L1) and interleukin (IL)-10 in the peripheral blood immunocytes of GC patients. Cancer tissues were obtained from patients who underwent surgical resection of GC, and stained sections of cancer tissues were visualized via confocal microscopy. The intestinal microbiome was analyzed using stool samples of healthy individuals and GC patients. Patient-derived avatar model was developed by injecting peripheral blood mononuclear cells (PBMCs) from advanced GC (AGC) patients into NSG mice, followed by injection of AGS cells. PD-L1 and IL-10 had higher expression levels in immune cells of GC patients than in those of healthy controls. The levels of immunosuppressive factors were increased in the immune and tumor cells of tumor tissues of GC patients. The abundances of Faecalibacterium and Bifidobacterium in the intestinal flora were lower in GC patients than in healthy individuals. Butyrate, a representative microbiome metabolite, suppressed the expression levels of PD-L1 and IL-10 in immune cells. In addition, the PBMCs of AGC patients showed increased levels of immunosuppressive factors in the avatar mouse model. Butyrate inhibited tumor growth in mice. Restoration of the intestinal microbiome and its metabolic functions inhibit tumor growth and reverse the immunosuppression due to increased PD-L1 and IL-10 levels in PBMCs and tumor cells of GC patients.

Uncovering the clinicopathological features of early recurrence after surgical resection of pancreatic cancer.

To identify risk factors and biomarker for early recurrence in patients diagnosed with pancreatic cancer who undergo curative resection. Early recurrence after curative resection of pancreatic cancer is an obstacle to long-term survival. We retrospectively reviewed 162 patients diagnosed with pancreatic cancer who underwent curative resection. Early recurrence was defined as recurrence within 12 months of surgery. We selected S100A2 as a biomarker and investigated its expression using immunohistochemistry. Of the total, 79.6% (n = 129) of patients received adjuvant chemotherapy after surgery and 117 (72.2%) experienced recurrence, of which 73 (45.1%) experience early recurrence. In multivariate analysis, age < 60 years, presence of lymph node metastasis, and no adjuvant chemotherapy were significantly associated with early recurrence (all P < 0.05). The proportion of patients with high S100A2 expression (H-score > 5) was significantly lower in the early recurrence group (41.5% vs. 63.3%, P = 0.020). The cumulative incidence rate of early recurrence was higher in patients with an S100A2 H-score < 5 (41.5% vs. 63.3%, P = 0.012). The median overall survival of patients with higher S100A2 expression was longer than those with lower S100A2 expression (median 30.1 months vs. 24.2 months, P = 0.003). High-risk factors for early recurrence after surgery for pancreatic cancer include young age, lymph node metastasis, and no adjuvant therapy. Neoadjuvant treatment or intensive adjuvant therapy after surgery may improve the prognosis of patients with high-risk signatures. In patients who receive adjuvant therapy, high S100A2 expression is a good predictor.

Apoptotic effect of tolfenamic acid on MDA-MB-231 breast cancer cells and xenograft tumors.

Recent studies have indicated that non-steroidal anti-inflammatory drug (NSAID), particularly tolfenamic acid, can inhibit proliferation and induce apoptosis invarious cancer cells. Breast cancer represents one-third of all cancers diagnosed in women and is the second leading cause of cancer death in Western European and North American women. In the present study, we investigated the apoptotic effect of tolfenamic acid in MDA-MB-231 estrogen receptor-negative human breast carcinoma cells and in a xenograft tumor model. Treatment of cells with tolfenamic acid significantly decreased cell viability in a concentration-dependent manner. Notably, tolfenamic acid increased apoptosis-related proteins, such as p53 and p21, within 48 h. Furthermore, in vivo experiments showed that tolfenamic acid treatment resulted in a significant reduction in tumor volume over 5 weeks. Immunohistochemistry results showed that apoptosis-related protein induction by tolfenamic acid was significantly higher in the 50 mg/kg-treated group compared to the control group. Together, these results indicate that tolfenamic acid induces apoptosis in MDA-MB-231 breast cancer cells and tumor xenograft model and it may be a potential chemotherapeutic agent against breast cancer.