High level of C3 is associated with Th2 immune response and liver fibrosis in patients with schistosomiasis.

Long-term infection of schistosomiasis will seriously affect the liver health of patients. The serum of 334 chronic Schistosoma japonicum patients and 149 healthy volunteers was collected. Compared with heathy people, the level of C4 (complement 4) was increased, and the level of C3 (complement 3) was in an obvious skewed distribution. ELISA was performed to detect the serum cytokines, the results showed that the levels of IFN-γ (interferon-γ), IL (interleukin)-2 and TNF-α (tumour necrosis factor-α) were reduced, while the levels of Th2 cytokines (IL-4, IL-6 and IL-10) were increased. In the serum of patients with high C3, the secretion of HA (hyaluronic acid), LN (laminin), IV-C (type IV collagen) and PCIII (type III procollagen) were increased, the activation of hepatic stellate cells was promoted. Exogenous human recombinant C3 made mice liver structure of the mice damaged and collagen deposition. IFN-γ and IFN-γ/IL-4 were decreased, while HA, LN, PCIII and IV-C were increased, and the expressions of α-SMA and TGF-ß1 in liver tissues were up-regulated. However, the addition of IFN-γ partially reversed the effect of C3 on promoting fibrosis. High level of C3 is associated with Th2 immune response and liver fibrosis in patients with schistosomiasis.

Serum anion gap at admission predicts all-cause mortality in critically ill patients with cerebral infarction: evidence from the MIMIC-III database.

BACKGROUND: Recent studies reported that serum anion gap could be regarded as a prognostic biomarker for patients admitted to intensive care units. However, the association between AG and mortality in cerebral infarction patients remained largely unknown. METHODS: Relevant clinical data were collected from Medical Information Mart for Intensive Care III. Patients were divided into three groups according to tertiles of AG. Kaplan-Meier curve and Cox proportional hazards models were used to evaluate the association between AG levels and all-cause mortality. Subgroup analyses were performed to verify the predictive role of AG on mortality. RESULTS: Kaplan-Meier analysis showed that patients with higher AG had shorter survival time. Cox regression model indicated high AG as an independent risk factor of 30-day, 60-day and 180-day all-cause mortality (30-day: HR = 2.45, 95% CI = 1.21-4.97, 60-day: HR = 2.04, 95% CI = 1.07-3.89, and 180-day: HR = 1.85, 95% CI = 1.02-3.36). However, no significance was observed between AG and 365-day all-cause mortality (HR = 1.56, 95% CI = 0.87-2.78). CONCLUSIONS: High AG was associated with increased risk of all-cause mortality, and AG could be an independent short-term prognostic factor for cerebral infarction.

Fast quantification of free amino acids in food by microfluidic voltage-assisted liquid desorption electrospray ionization-tandem mass spectrometry.

A method based on microfluidic voltage-assisted liquid desorption electrospray ionization-tandem mass spectrometry (VAL-DESI-MS/MS) has been developed for fast quantification of free amino acids in food. Food extracts were transferred to the microfluidic platform and analyzed by liquid desorption ESI-MS/MS. Deuterated aspartic acid (i.e., 2,2,3-d3-Asp) was used as internal standard for analysis. The method had linear calibration curves with r2 values > 0.998. Limits of detection were at the level of sub µM for the amino acids tested, i.e., glutamic acid (Glu), arginine (Arg), tyrosine (Tyr), tryptophan (Trp), and phenylalanine (Phe). To validate the proposed method in food analysis, extracts of Cordyceps fungi were analyzed. Amino acid contents were found in the range from 0.63 mg/g (Tyr in Cordyceps sinensis) to 4.44 mg/g (Glu in Cordyceps militaris). Assay repeatability (RSD) was ≤ 5.2% for all the five amino acids measured in all the samples analyzed. Recovery was found in the range from 95.8 to 105.1% at two spiking concentrations of 0.250 mg/g and 1.00 mg/g. These results prove that the proposed microfluidic VAL-DESI-MS/MS method offers a quick and convenient means of quantifying free amino acids with accuracy and repeatability. Therefore, it may have potential in food analysis for nutritional and quality assessment purposes. Graphical abstract.

microRNA-21 promotes breast cancer proliferation and metastasis by targeting LZTFL1.

BACKGROUND: Breast cancer is the most common cancer type in female. As microRNAs play vital role in breast cancer, this study aimed to explore the molecular mechanism and clinical value of miR-21 in breast cancer. METHODS: qRT-PCR was performed to detect miR-21 levels in plasma of 127 healthy controls, 82 benign breast tumor, 252 breast cancer patients, as well as in breast cancer cell lines. Transwell and wound healing assay were used to analyze breast cancer metastasis in response to miR-21 inhibitor. Colony formation and eFluor™ 670 based flow cytometric analysis were used to test breast cancer proliferation following miR-21 inhibitor treatment. Leucine zipper transcription factor-like 1 (LZTFL1), the target gene of miR-21 was predicted by MIRDB, TargetScan 5.1, PicTar and miRanda. Survival analysis of LZTFL1 levels in breast cancer prognosis was estimated with the Kaplan-Meier method by log-rank test according to data from the Cancer Genome Atlas. Luciferase activity assay was performed to confirm the regulation of miR-21 on LZTFL1. LZTFL1 siRNA and miR-21 inhibitor were co-transfected to breast cancer cells, then cell proliferation, migration and epithelial-mesenchymal transition (EMT) makers were tested. BALB/c nude mice were injected in situ with Hs578T cells stably overexpressing miR-21. Breast tumor growth, metastasis and the expression of EMT markers or LZTFL1 were detected in vivo. RESULTS: Plasma miR-21 levels were elevated in breast cancer patients compared with healthy controls and benign breast tumor patients, and the miR-21 levels were significantly decreased after surgery comparing with pre operation in 44 patients. Inhibition of miR-21 suppressed cell proliferation and metastasis in breast cancer cells. LZTFL1 was identified as a novel target gene of miR-21. Knockdown of LZTFL1 overcame the suppression of miR-21 inhibitor on cell proliferation, metastasis and the expression of EMT markers in breast cancer cells. miR-21 overexpression promoted breast cancer cell proliferation and metastasis in vivo. CONCLUSIONS: These results indicate that plasma miR-21 level is a crucial biomarker for breast cancer diagnosis and targeting miR-21-LZTFL1-EMT axis might be a promising strategy in breast cancer therapy. TRIAL REGISTRATION: Retrospectively registered.

Long noncoding RNA ROR promotes breast cancer by regulating the TGF-ß pathway.

BACKGROUND: Breast cancer is the leading cause of oncological mortality among women. Efficient detection of cancer cells in an early stage and potent therapeutic agents targeting metastatic tumors are highly needed to improve survival rates. Emerging evidence indicates that lncRNAs (long noncoding RNAs) are critical regulators of fundamental cellular processes in a variety of tumors including breast cancer. The functional details of these regulatory elements, however, remain largely unexplored. METHODS: In this study, lncRNA ROR (linc-ROR) was examined by real-time PCR in different breast cancer cell lines and breast tumor tissues/non-tumor tissues were collected from both breast cancer patients and healthy controls. Linc-ROR was knockdown in breast cancer cell lines and the effects on cell proliferation, migration and invasion were tested both in vitro and in vivo tumor model. Effects of linc-ROR knockdown on TGF-ß signaling pathway were investigated by Western blot. RESULTS: Our studies have suggested that linc-ROR, a critical factor for embryonic stem cell maintenance, probably acts as an oncogenic factor in breast cancer cells, causing poor prognostic outcomes. Overexpression of linc-ROR seems to be responsible for promoting proliferation and invasion of cancer cells as well as tumor growth in nude mice. The regulatory action of linc-ROR can affect the activity of the TGF-ß signaling pathway, which has been proven critical for mammary development and breast cancer. CONCLUSIONS: The results have highlighted the potential importance of linc-ROR in the progression of advanced breast cancer, and thus will stimulate efforts in the development of novel diagnostic and therapeutic strategies.

Peripheral Blood Leukocyte Expression of lncRNA MIAT and Its Diagnostic and Prognostic Value in Ischemic Stroke.

BACKGROUND: Ischemic stroke (IS) is an extremely heterogeneous disease with variable pathogenesis. Due to the lack of early diagnostic markers, the mortality rate of IS remains high. Cumulative evidence shows that long noncoding RNAs among noncoding RNAs play important roles in cardiovascular diseases. In the present study, we focused on the expression pattern of myocardial infarction-associated transcript (MIAT) and its clinical significance in IS. METHODS: Blood samples were obtained from IS patients (n = 189) and healthy controls (n = 189). The National Institutes of Health Stroke Scale (NIHSS) was measured at the time of admission. Short-term functional outcome was measured by the modified Rankin Scale (mRS) at 3 months after admission. Multivariate analyses were performed using logistic regression models. The receiver operating characteristic (ROC) curve was used to evaluate the accuracy of MIAT in the diagnosis and prognosis of IS. RESULTS: In IS patients, MIAT expression level was significantly upregulated and correlated with NIHSS scores (r = .421, P <.001), mRS (r = .339, P <.001), high-sensitivity C-reactive protein (r = .309, P <.001), and infarct volume (r = .318, P <.001). ROC curves indicated that MIAT could serve as a potential marker for discriminating IS patients from the controls with an area under the curve of .842 (95% confidence interval, .802-.881). The overall survival analysis showed that patients with higher MIAT expression had a relatively poor prognosis. Meanwhile, the multivariate analysis revealed that MIAT was an independent prognostic marker of functional outcome and death in patients with IS. CONCLUSION: Our data suggested that MIAT might be a potential diagnostic and prognostic indicator in IS.

Differential expression of plasma microRNA-125b in hepatitis B virus-related liver diseases and diagnostic potential for hepatitis B virus-induced hepatocellular carcinoma.

AIM: Acting as a tumor suppressor, microRNA (miR)-125b shows aberrant low expression in hepatocellular carcinoma (HCC), and researchers have found that its dysregulation has a close relationship with hepatitis B virus (HBV) infection. Here, we investigated the expression profile of this miRNA in the plasma of healthy subjects and patients with chronic HBV-related liver diseases in order to confirm the feasibility of this circulating miRNA as a differential diagnostic biomarker for HBV-induced HCC (HBV-HCC). METHODS: A total of 242 individuals were enrolled in this study. The expression levels of plasma miR-125b were examined using quantitative real-time polymerase chain reaction technology. RESULTS: The levels of plasma miR-125b were remarkably decreased in HBV-HCC patients compared to healthy controls and HBV subjects without HCC (all P < 0.001), and the low plasma miR-125b levels in HBV-HCC patients were associated with higher prevalence of metastasis (P = 0.021). The receiver-operating characteristic curve analyses indicated that plasma miR-125b presented a high accuracy (area under the curve = 0.891, 0.958, 0.958) for diagnosing HBV-HCC cases from healthy controls and patients with chronic hepatitis B and HBV-related liver cirrhosis, respectively. In addition, our study found that the expression levels of plasma miR-125b in HBV patients without HCC were higher than those in healthy subjects (P < 0.001); it yielded an area under the curve of 0.691 in discriminating patients with chronic HBV infection who were negative for HCC from healthy controls. CONCLUSION: The measurement of plasma-based miR-125b holds promise as a diagnostic marker for HBV-HCC differential diagnosis and for chronic HBV viral infection. Those HBV-infected individuals with increased risk of HCC would be detected early through monitoring the changes in this circulating miRNA.

Prognostic and Diagnostic Significance of SDPR-Cavin-2 in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor worldwide. Due to the lack of early prediction marker, numerous patients were diagnosed in their late stage. The family of cavins plays important roles in caveolae formation and cellular processes. Cavin-2, one of the members of cavins, has been reported as a suppresser in cancers. In this study, we have investigated its expression pattern and clinical significance in HCC. METHODS: RT­qPCR was performed to detect the expression of cavin-2. RESULTS: Cavin-2 was down-regulated in HCC and associated with tumor differentiation (r=-0.275, P=0.013) and tumor-node-metastasis (TNM) stage (r=-0.216, P=0.035). The Overall survival analysis showed that patients with lower cavin-2 expression had a relatively poor prognosis. Meanwhile, the multivariate analysis revealed that cavin-2 was an independent prognostic factor. The receiver operating characteristic curve analyses indicated that plasma cavin-2 presented a high accuracy (AUC=0.727, 0.865, 0.901) for diagnosing HCC cases from controls, hepatitis B and cirrhosis patients, respectively. Meanwhile, plasma cavin-2 showed a high sensitivity (88.4%, 89.9%) for detecting HCC with the serum α­fetoprotein (AFP) levels below 200 ng/ml from those hepatitis B and cirrhosis cases. CONCLUSION: Our data suggested that cavin-2 might be considered as a potential prognostic and diagnostic indicator in HCC.

Diagnostic Potential of Differentially Expressed Homer1 and Homer2 in Ischemic Stroke.

BACKGROUND: Ischemic stroke (IS) is an extremely heterogeneous disease with variable pathogenesis. Due to the lack of early diagnostic marker, the mortality rate of IS remains high worldwide. The family of Homer plays an important role in the pathology of atherosclerotic plaque. In this study, we have investigated its expression pattern and clinical significance in IS. METHODS: RT-qPCR was performed to detect the expression of Homer1, Homer2, and Homer3. RESULTS: We found that the mRNA levels of Homer1 (p<0.001) and Homer2 (p<0.001), but not Homer3, in large-artery atherosclerosis (LAA) strokes were significantly upregulated than those in non-LAA strokes and controls. Multinomial logistic regression analyses showed that, although none of the Homer was associated with non-LAA strokes, higher Homer1 (adjusted OR=1.337, 95% CI: 1.227-1.458) and Homer2 (adjusted OR=1.099, 95% CI: 1.062-1.138) levels showed significant associations with increased odds of having LAA stroke, compared with the controls. The receiver operating characteristic (ROC) curves showed that the combination of Homer1 and Homer2 had a better diagnostic accuracy to differentiate LAA strokes from non-LAA strokes and controls, and the sensitivity and specificity ratios were 80.5%/90.4% and 98.0%/70.3%, respectively. CONCLUSION: Our data suggested that Homer1 and Homer2 might be considered as novel diagnostic biomarkers for LAA stroke.

In-hospital free fatty acids levels predict the severity of myocardial ischemia of acute coronary syndrome.

BACKGROUND: We aimed to assess whether the levels of FFAs (free fatty acids) in ACS (acute coronary syndrome) patients depend on the extent of myocardial ischemia during the subacute phase of ACS attack. METHODS: A total of 892 consecutive CAD (coronary artery disease) subjects undergoing coronary angiography were enrolled. The FFAs contents were measured based on enzymatic assay. The relationship between FFAs and Gensini score and ACS susceptibility was assessed. RESULTS: In the overall population, the upper FFAs quartile was accompanied with higher ischemia parameters and increased occurrence of ACS and STEMI (ST-segment elevation myocardial infarction) (P < 0.05). The FFAs concentrations were approximately 1.5-fold higher in ACS than in stable CAD patients, roughly 1.3-fold higher in STEMI than non-STEMI ACS patients and probably 1.3-fold higher in non-STEMI ACS than in stable CAD patients. After adjusted for traditional cardiovascular risk factors, the FFAs level remained a risk factor for a higher Gensini score with more than 40 (P < 0.001) and prevalent ACS (P < 0.001). After adjusted for traditional risk factors, FFAs levels after natural logarithm transformation were associated with hs-CRP and WBC counts in ACS patients. A multiplicative interaction was found between hs-CRP, WBC counts and FFAs in incident ACS and higher Gensini score (P < 0.001). CONCLUSIONS: Higher in-hospital levels of FFAs persist and may reflect the severity of ischemia and necrosis during the subacute phase of ACS attack.

Expression of polycystins and fibrocystin on primary cilia of lung cells.

Mutations in polycystin-1, polycystin-2, or fibrocystin account for autosomal dominant or recessive polycystic kidney disease. Renal cystogenesis is linked to abnormal localization and function of these cystoproteins in renal primary cilia. They are also expressed in extrarenal tissues in which their functions are unclear. Here we found that human type-II alveolar epithelial A549, airway submucosal Calu-3 cells, and rat bronchioles contain primary or multiple cilia in which we detected these cystoproteins. At sub-confluency, polycystin-1 was expressed on plasma membrane, while polycystin-2 was localized to the ER of resting cells. Both polycystins were detected on the spindle and mid-body of mitotic cells, while fibrocystin was on centrosome throughout cell cycle. Polycystins and fibrocystin may participate in regulating mucociliary sensing and transport within pulmonary airways.

Association between serum free fatty acid levels and possible related factors in patients with type 2 diabetes mellitus and acute myocardial infarction.

BACKGROUND: Free fatty acids (FFAs) play importance roles in the development of diabetes and cardiovascular diseases. We measured serum FFA levels from type 2 diabetes mellitus (T2DM) and acute myocardial infarction (AMI) patients and assay the correlation between serum FFA levels and related factors. The present study was undertaken to investigate a possible relation between the changes in serum free fatty acid concentration with acute myocardial infarction and type 2 diabetes mellitus. METHODS: The study population consisted of 540 healthy individuals and 103 patients with T2DM, 59 patients with AMI and 21 volunteers. Serum FFAs were measured with high pressure liquid chromatography. Blood urea nitrogen and uric acid were measured in clinical laboratory, as were glycemic, lipid and blood routine parameters. We selected 242 individuals with age over 60 years, 143 healthy individuals and 52 patients with T2DM, 47 patients with AMI were incorporated into three groups as control group, T2DM group and AMI group. Associations were analyzed with stepwise regression analysis with adjusted for age, sex, body mass index. RESULTS: Serum FFA levels were significantly higher in the age over 60 years individuals compared to 20 ~ 50 years (logFFA µmmol/L:2.60 ± 0.16 vs. 2.73 ± 0.18, P < .001) in the healthy group. We found lower FFA levels in the AMI compared to the T2DM and control group (2.64 ± 0.22 vs. 2.72 ± 0.13&2.72 ± 0.16, respectively, P < .05&P < 0.01) in the age over 60, fasting blood glucose level higher in the AMI and T2DM (5.78 ± 1.32&7.75 ± 2.93 mmol/L vs. 4.90 ± 0.47 mmol/L, P < .01&P < .001) compared with the normal group, HDL level (1.01 ± 0.22&0.98 ± 0.18 mmol/L vs.1.30 ± 0.22 mmol/L, P < .001&P < .001). With stepwise regression analysis, the serum FFA levels was positively associated with the HDL in the control group (YlogFFA = 2.32 + 0.33XHDL, R = 0.26, P < .01) and T2MD (YlogFFA = 2.46 + 0.27XHDL, R = 0.36, P < .05), AST in AMI (YlogFFA =2.24 + 0. 015XAST, R = 0.49, P < .01). CONCLUSIONS: Compared to control group, serum FFA levels were decreased only in AMI group, while HDL level was increased in both AMI and T2DM group. The serum FFA levels were positive association with the HDL level in both T2DM and control group, FFA levels were positive association with AST in AMI.

Diagnostic potential of differentially expressed Homer1, IL-1ß, and TNF-α in coronary artery disease.

Increasing evidences suggest that inflammation plays an important role in the pathogenesis of coronary artery disease (CAD). Numerous inflammatory cytokines and related genes mediate adverse cardiovascular events in patients with CAD, such as interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and Homer in the present study. The study was carried out on 163 CAD patients at different stages and 68 controls. The gene expression of Homer1, Homer2, Homer3, IL-1ß, and TNF-α in the peripheral blood leukocytes were measured by real-time polymerase chain reaction. The mRNA levels of Homer1, IL-1ß, and TNF-α in CAD patients were significantly higher than those in the control group, but not Homer2 and Homer3. However, there was no considerable difference in the mRNA levels of Homer1, IL-1ß, and TNF-α among AMI, UAP, and SAP three subgroups of CAD. The receiver operating characteristic (ROC) curves showed that Homer1 had a better diagnostic value for UAP patients compared with IL-1ß and TNF-α. Like IL-1ß and TNF-α, Homer1 may also be an important participant of atherosclerotic plaque development and eventually rupture. The results of the present study may provide an important basis for diagnosing CAD patients, and provide new therapeutic targets for CAD.

Receptor for activated C kinase 1 (RACK1) inhibits function of transient receptor potential (TRP)-type channel Pkd2L1 through physical interaction.

Pkd2L1 (also called TRPP3) is a non-selective cation channel permeable to Ca(2+), Na(+), and K(+) and is activated by Ca(2+). It is also part of an acid-triggered off-response cation channel complex. We previously reported roles of the Pkd2L1 C-terminal fragments in its channel function, but the role of the N terminus remains unclear. Using a yeast two-hybrid screening, we found that the Pkd2L1 N terminus interacts with the receptor for activated C kinase 1 (RACK1), a scaffolding/anchoring protein implicated in various cellular functions. This interaction requires the last two Trp-Asp (WD) motifs of RACK1 and fragment Ala(19)-Pro(45) of Pkd2L1. The interaction was confirmed by GST pulldown, blot overlay, and co-immunoprecipitation assays. By (45)Ca tracer uptake and two-microelectrode voltage clamp electrophysiology, we found that in Xenopus oocytes with RACK1 overexpression Pkd2L1 channel activity is abolished or substantially reduced. Combining with oocyte surface biotinylation experiments, we demonstrated that RACK1 inhibits the function of Pkd2L1 channel on the plasma membrane in addition to reducing its total and plasma membrane expression. Overexpressing Pkd2L1 N- or C-terminal fragments as potential blocking peptides for the Pkd2L1-RACK1 interaction, we found that Pkd2L1 N-terminal fragment Met(1)-Pro(45), but not Ile(40)-Ile(97) or C-terminal fragments, abolishes the inhibition of Pkd2L1 channel by overexpressed and oocyte-native RACK1 likely through disrupting the Pkd2L1-RACK1 association. Taken together, our study demonstrated that RACK1 inhibits Pkd2L1 channel function through binding to domain Met(1)-Pro(45) of Pkd2L1. Thus, Pkd2L1 is a novel target channel whose function is regulated by the versatile scaffolding protein RACK1.

The clinical significance of HER-2 and NF-KB expression in gastric cancer.

BACKGROUND/AIMS: To investigate the expression of human epidermal growth factor 2 (HER-2) and Nuclear factor-Kb (NF-KB) in gastric cancer, and the relation of these two parameters with stage, grade and metastasis of gastric cancer. METHODOLOGY: The serum level of HER-2 in 75 gastric cancer patients and control participants were determined by enzyme-linked immunosorbent assay (ELISA) kits. Expression of HER-2 and NF-KB protein were detected by immunohistochemical staining (SP method) of paraffin-embedded tissues in 75 tumors (observed group) and 22 normal gastric specimens. The clinical pathological data was statistically analyzed. RESULTS: Serum HER-2 level were significantly increased in study group compared with those in the control group (p<0.001). The HER-2 level of 8.2 ng/mL as the cutoff value has a 79% sensitivity and an 82% specificity for predicting gastric cancer. The positive rate of HER-2 and NF-KB in the observed group was 24.00% (18/75) and 62.67% (47/75) respectively. The expression of HER-2 and NF-KB were not correlated with age and gender, but with stage, grade and metastasis (p<0.05). The expression of NF-KB was correlated with tumor size (p<0.05), while HER-2 was not (p<0.05). When HER-2 was positive, N F-KB had a positive rate of 94.44% (17/18), but a positive rate of 52.63% (30/57) when HER-2 was negative. Expression of NF-KB in gastric cancer tissue was correlated with HER-2 expression (X2 = 8.514, p<0.01). CONCLUSIONS: These data suggest that the expression of NF-KB in gastric cancer tissue is correlated with HER-2 expression, and they may play a very important role in the progress of gastric cancer.

N6-methyladenosine RNA modification in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, influencing numerous regulatory axes and extrahepatic vital organs. The molecular mechanisms that lead to the progression of NAFLD remain unclear and knowledge on the pathways causing hepatocellular damage followed by lipid accumulation is limited. Recently, a number of studies have shown that mRNA N6-methyladenosine (m6A) modification contributes to the progression of NAFLD. In this review, we summarize current knowledge on m6A modification in the metabolic processes associated with NAFLD and discuss the challenges of and prospects for therapeutic avenues based on m6A regulation for the treatment of liver disease.

FKBP11 upregulation promotes proliferation and migration in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related deaths world over. Early diagnosis and effective treatment monitoring significantly improves patients' outcomes. FKBP11 gene is highly expressed in HCC and could play a role in its development, early diagnosis and treatment. OBJECTIVE: This study aimed to evaluate the expression of FKBP11 in HCC, its correlation with patients' clinical characteristics and potential role in HCC development. METHODS: Expression was determined by bioinformatics analysis, quantitative real-time PCR, western blot, and immunohistochemistry. CCK-8, Transwell and wound healing assays were used to investigate involvement in HCC development. RESULTS: FKBP11 was significantly upregulated in HCC cells, tissues and blood (all p< 0.001). Its receiver operator characteristic (ROC) curve had an AUC of 0.864 (95% CI: 0.823-0.904), at a sensitivity of 0.86 and specificity of 0.78 indicating a good diagnostic potential in HCC. Its expression was markedly reduced after surgery (p< 0.0001), indicating a potential application in HCC treatment follow-up. Knockdown of FKBP11 in HCC cells attenuated proliferation and migration, suggesting a possible role in HCC pathogenesis. CONCLUSION: This study thus found that FKBP11 is upregulated in HCC, and the upregulation promotes HCC development. FKBP11 levels are significantly reduced post-surgery and could be a potential diagnostic and prognostic marker for HCC.

Glutamine metabolism in breast cancer and possible therapeutic targets.

Cancer is characterized by metabolic reprogramming, which is a hot topic in tumor treatment research. Cancer cells alter metabolic pathways to promote their growth, and the common purpose of these altered metabolic pathways is to adapt the metabolic state to the uncontrolled proliferation of cancer cells. Most cancer cells in a state of nonhypoxia will increase the uptake of glucose and produce lactate, called the Warburg effect. Increased glucose consumption is used as a carbon source to support cell proliferation, including nucleotide, lipid and protein synthesis. In the Warburg effect, pyruvate dehydrogenase activity decreases, thereby disrupting the TCA cycle. In addition to glucose, glutamine is also an important nutrient for the growth and proliferation of cancer cells, an important carbon bank and nitrogen bank for the growth and proliferation of cancer cells, providing ribose, nonessential amino acids, citrate, and glycerin necessary for cancer cell growth and proliferation and compensating for the reduction in oxidative phosphorylation pathways in cancer cells caused by the Warburg effect. In human plasma, glutamine is the most abundant amino acid. Normal cells produce glutamine via glutamine synthase (GLS), but the glutamine synthesized by tumor cells is insufficient to meet their high growth needs, resulting in a "glutamine-dependent phenomenon." Most cancers have an increased glutamine demand, including breast cancer. Metabolic reprogramming not only enables tumor cells to maintain the reduction-oxidation (redox) balance and commit resources to biosynthesis but also establishes heterogeneous metabolic phenotypes of tumor cells that are distinct from those of nontumor cells. Thus, targeting the metabolic differences between tumor and nontumor cells may be a promising and novel anticancer strategy. Glutamine metabolic compartments have emerged as promising candidates, especially in TNBC and drug-resistant breast cancer. In this review, the latest discoveries of breast cancer and glutamine metabolism are discussed, novel treatment methods based on amino acid transporters and glutaminase are discussed, and the relationship between glutamine metabolism and breast cancer metastasis, drug resistance, tumor immunity and ferroptosis are explained, which provides new ideas for the clinical treatment of breast cancer.

Research progress of the application of mesenchymal stem cells in chronic inflammatory systemic diseases.

Chronic inflammatory systemic diseases are the result of the body's immune imbalance, with a long course and recurring episodes. Immunosuppressants are the main treatment, but not all patients respond well to it. Being capable of both self-renewal and differentiation into multiple tissue cells and low immunogenicity, mesenchymal stem cell is a promising treatment for chronic inflammatory systemic diseases. In this article, we describe the research progress and clinical application of mesenchymal stem cells in chronic inflammatory systemic diseases and look for influencing factors and biomarkers that can predict the outcome of patient with mesenchymal stem cell transplantation.

Comprehensive Analysis Identified ASF1B as an Independent Prognostic Factor for HBV-Infected Hepatocellular Carcinoma.

Purpose: Hepatitis B (HBV)-infected hepatocellular carcinoma is one of the most common cancers, and it has high incidence and mortality rates worldwide. The incidence of hepatocellular carcinoma has been increasing in recent years, and existing treatment modalities do not significantly improve prognosis. Therefore, it is important to find a biomarker that can accurately predict prognosis. Methods: This study was analyzed using the The Cancer Genome Atlas (TCGA) database and validated by the International Cancer Genome Consortium (ICGC) database. The STRING database was used to construct a gene co-expression network and visualize its functional clustering using Cytoscape. A prognostic signature model was constructed to observe high and low risk with prognosis, and independent prognostic factors for HBV-infected hepatocellular carcinoma were identified by Cox regression analysis. The independent prognostic factors were then analyzed for expression and survival, and their pathway enrichment was analyzed using gene set enrichment analysis (GSEA). Results: 805 differentially expressed genes (DEGs) were obtained by differential analysis. Protein-protein interaction (PPI) showed that DEGs were mostly clustered in functional modules, such as cellular matrix response, cell differentiation, and tissue development. Prognostic characterization models showed that the high-risk group was associated with poor prognosis, while Cox regression analysis identified ASF1B as the only independent prognostic factor. As verified by expression and prognosis, ASF1B was highly expressed in HBV-infected hepatocellular carcinoma and led to a poor prognosis. GSEA showed that high ASF1B expression was involved in cell cycle-related signaling pathways. Conclusion: Bioinformatic analysis identified ASF1B as an independent prognostic factor in HBV-infected hepatocellular carcinoma, and its high expression led to a poor prognosis. Furthermore, it may promote hepatocellular carcinoma progression by affecting cell cycle-related signaling pathways.