Deciphering the role of non-coding RNAs involved in sorafenib resistance.

Sorafenib is an important treatment strategy for advanced hepatocellular carcinoma (HCC). Unfortunately, drug resistance has become a major obstacle in sorafenib application. In this study, whole transcriptome sequencing (WTS) was conducted to compare the paired differences between non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and mRNAs, in sorafenib-resistant and parental cells. The overlap of differentially expressed ncRNAs (DENs) between the SMMC7721/S and Huh7/S cells and their parental cells was determined. 2 upregulated and 3 downregulated lncRNAs, 2 upregulated and 1 downregulated circRNAs, as well as 10 upregulated and 2 downregulated miRNAs, in both SMMC7721/S and Huh7/S cells, attracted more attention. The target genes of these DENs were then identified as the overlaps between the differentially expressed mRNAs achieved using the WTS analysis and the predicted genes of DENs obtained using the "co-localization" or "co-expression," miRanda, and RNAhybrid analysis. Consequently, the potential regulatory network between overlapping DENs and their target genes in both SMMC7721/S and Huh7/S cells was explored. The "lncRNA-miRNA-mRNA" and "circRNA-miRNA-mRNA" networks were constructed based on the competitive endogenous RNA (ceRNA) theory using the Cytoscape software. In particular, lncRNA MED17-203-miRNA (miR-193a-5p, miR-197-3p, miR-27a-5p, miR-320b, miR-767-3p, miR-767-5p, miR-92a-3p, let-7c-5p)-mRNA," "circ_0002874-miR-27a-5p-mRNA" and "circ_0078607-miR-320b-mRNA" networks were first introduced in sorafenib-resistant HCC. Furthermore, these networks were most probably connected to the process of metabolic reprogramming, where the activation of the PPAR, HIF-1, Hippo, and TGF-ß signaling pathways is governed. Alternatively, the network "circ_0002874-miR-27a-5p-mRNA" was also involved in the regulation of the activation of TGF-ß signaling pathways, thus advancing Epithelial-mesenchymal transition (EMT). These findings provide a theoretical basis for exploring the mechanisms underlying sorafenib resistance mediated by metabolic reprogramming and EMT in HCC.

Involvement of the ABCB1 C3435T Variant but Not the MTHFR C677T or MTHFR A1298C Variant in High-Dose Methotrexate-Induced Toxicity in Pediatric Acute Lymphoblastic Leukemia Patients in China.

Purpose: It remains unclear whether the MTHFR C677T, MTHFR A1298C and ABCB1 C3435T genetic variants are associated with methotrexate (MTX) elimination delay and high-dose MTX (HD-MTX) toxicities in the treatment of pediatric acute lymphoblastic leukemia (ALL). The aim of our study was to analyze the potential predictive role of MTHFR C677T, MTHFR A1298C and ABCB1 C3435T in toxicities and the relationship between these variants and MTX elimination delay during HD-MTX therapy in pediatric ALL patients. Patients and Methods: We conducted a retrospective study on ALL patients receiving HD-MTX treatment with available MTHFR C677T, MTHFR A1298C and ABCB1 C3435T genotype and 44-h plasma MTX levels. Logistic regression analyses and chi-square tests were used to assess the relationship between the variants and HD-MTX toxicities and MTX elimination delay. Results: Genotype frequencies were in Hardy-Weinberg equilibrium. MTX elimination delay did not significantly differ between MTHFR C677T and MTHFR A1298C or ABCB1 C3435T. Leukopenia (P=0.028), neutropenia (P=0.034) and oral mucositis (P=0.023) were 6.444-fold, 4.978-fold and 9.643-fold increased, respectively, in ABCB1 C3435T homozygous genotype (TT) patients compared to wild-type (CC) patients. No significant association was found between the toxicities investigated and MTHFR C677T or MTHFR A1298C. Conclusion: This study showed that the ABCB1 C3435T homozygous allele genotype (TT) is associated with increased MTX-related toxicities (leukopenia, neutropenia and oral mucositis). These results may help to distinguish pediatric ALL patients with a relatively high risk of MTX-related toxicities before HD-MTX infusion and optimize MTX treatment.

Ubenimex suppresses glycolysis mediated by CD13/Hedgehog signaling to enhance the effect of cisplatin in liver cancer.

Background: Liver cancer ranks third in fatalities among all cancer-related deaths. As a traditional chemotherapy drug, the application of cis-Diamminedichloroplatinum (II) (cisplatin, CDDP) for the treatment of liver cancer is greatly limited by its side effects and high drug resistance. Therefore, we are in urgent need of a more effective and less toxic CDDP therapeutic regimen. Our research aimed to clarify the possible mechanism of ubenimex in enhancing the effect of CDDP on liver cancer. Methods: The underlying mechanism was determined using Cell Counting Kit-8 (CCK-8) assay, flow cytometry, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), transwell assay, wound healing assay and western blot assay. Results: The data indicated that ubenimex suppressed the expression levels of glycolysis-related proteins by decreasing the expression levels of cluster of differentiation 13 (CD13), while overexpression of CD13 could restore the activity of glycolysis. The glycolysis inhibitor 2-deoxy-D-glucose enhanced the antiproliferative effect of ubenimex and CDDP. In addition, the inhibition of the activity levels of the Hedgehog (Hh) pathway members was accompanied by a decrease in CD13 expression, which was reversed following CD13 overexpression. Moreover, ubenimex inhibited the production of lactic acid and adenosine triphosphate (ATP), as well as the expression of key proteins involved in glycolysis, which was similar to the effects caused by the Hh inhibitor cyclopamine. However, the effects of ubenimex were mediated by targeting CD13, while cyclopamine exhibited no effects on CD13, suggesting that Hh signaling occurred in the downstream of CD13. The inhibition of glycolysis by cyclopamine was reduced following CD13 overexpression, which further indicated that ubenimex targeted the CD13/Hh pathway to inhibit glycolysis. Finally, wound healing and transwell assays and cell proliferation and apoptosis analysis demonstrated that ubenimex inhibited glycolysis by alleviating the CD13/Hh pathway, which in turn enhanced the effects of CDDP on inhibiting the progression of liver cancer. Conclusions: Ubenimex inhibits glycolysis by targeting the CD13/Hh pathway, thus playing an anti-tumor role together with CDDP. This study demonstrated the adjuvant effect of ubenimex from the perspective of Hh signal-dependent glycolysis regulation.

Combating drug resistance in hepatocellular carcinoma: No awareness today, no action tomorrow.

Hepatocellular carcinoma (HCC), the sixth most common cancer worldwide, is associated with a high degree of malignancy and poor prognosis. Patients with early HCC may benefit from surgical resection to remove tumor tissue and a margin of healthy tissue surrounding it. Unfortunately, most patients with HCC are diagnosed at an advanced or distant stage, at which point resection is not feasible. Systemic therapy is now routinely prescribed to patients with advanced HCC; however, drug resistance has become a major obstacle to the treatment of HCC and exploring purported mechanisms promoting drug resistance remains a challenge. Here, we focus on the determinants of drug resistance from the perspective of non-coding RNAs (ncRNAs), liver cancer stem cells (LCSCs), autophagy, epithelial-mesenchymal transition (EMT), exosomes, ferroptosis, and the tumor microenvironment (TME), with the aim to provide new insights into HCC treatment.

A glance at transient hyperammonemia of the newborn: Pathophysiology, diagnosis, and treatment: A review.

Hyperammonemia is the excessive accumulation of ammonia in the blood, and is usually defined as a plasma level above 100 µmol/L in neonates or above 50 µmol/L in term infants, children, and adolescents. Patients with hyperammonemia usually experience life-threatening neuropsychiatric symptoms, especially newborns. It is routinely caused by inherited metabolic diseases and also by acquired disorders, such as liver failure, portosystemic shunting, gastrointestinal hemorrhage, ureterosigmoidostomy, renal tubular acidosis, hypoxic ischemic encephalopathy, infections with urea-metabolizing organisms, and some drugs. Transient hyperammonemia of the newborn (THAN) is a special type of hyperammonemia acknowledged in the field of metabolic disease as an inwell-defined or well-understood entity, which can be diagnosed only after the exclusion of genetic and acquired causes of hyperammonemia. Although the prognosis for THAN is good, timely identification and treatment are essential. Currently, THAN is underdiagnosed and much less is mentioned for early diagnosis and vigorous treatment. Herein, we present common themes that emerge from the pathogenesis, diagnosis, and management of THAN, based on current evidence. When a newborn presents with sepsis, intracranial hemorrhage, or asphyxia that cannot explain coma and seizures, doctors should always keep this disease in mind.

Drug Resistance in Cancers: A Free Pass for Bullying.

The cancer burden continues to grow globally, and drug resistance remains a substantial challenge in cancer therapy. It is well established that cancerous cells with clonal dysplasia generate the same carcinogenic lesions. Tumor cells pass on genetic templates to subsequent generations in evolutionary terms and exhibit drug resistance simply by accumulating genetic alterations. However, recent evidence has implied that tumor cells accumulate genetic alterations by progressively adapting. As a result, intratumor heterogeneity (ITH) is generated due to genetically distinct subclonal populations of cells coexisting. The genetic adaptive mechanisms of action of ITH include activating "cellular plasticity", through which tumor cells create a tumor-supportive microenvironment in which they can proliferate and cause increased damage. These highly plastic cells are located in the tumor microenvironment (TME) and undergo extreme changes to resist therapeutic drugs. Accordingly, the underlying mechanisms involved in drug resistance have been re-evaluated. Herein, we will reveal new themes emerging from initial studies of drug resistance and outline the findings regarding drug resistance from the perspective of the TME; the themes include exosomes, metabolic reprogramming, protein glycosylation and autophagy, and the relates studies aim to provide new targets and strategies for reversing drug resistance in cancers.

Sinus arrhythmia caused by pemetrexed with carboplatin combination: A case report.

Combination chemotherapy of pemetrexed and carboplatin is a standard treatment approach for non-small cell lung cancer (NSCLC). However, no prior reports have described cardiotoxicity associated with this therapeutic combination or sinus arrhythmia in oncological contexts. Here, we report the case of a 44-year-old female NSCLC patient that suffered from sinus arrhythmia following combined chemotherapeutic treatment with pemetrexed and carboplatin. The patient was successfully treated under medical guidance, and the condition was effectively reversed following the discontinuation of this chemotherapeutic regimen and medication prescribing. Overall, this represents a rare case of sinus arrhythmia in NSCLC patient during the first cycle of combined chemotherapy with pemetrexed and carboplatin. However, a putative etiological basis for this rare clinical entity remains to be established.

CD13 downregulation mediated by ubenimex inhibits autophagy to overcome 5-FU resistance by disturbing the EMP3/FAK/NF-κB pathway in gastric cancer cells.

Background: Gastric cancer (GC) is one of the most common malignant tumours in China, but the efficacy of chemotherapy on GC is significantly reduced due to the occurrence of drug resistance. Some studies have shown that the expression level of CD13 is associated with tumour resistance, but whether ubenimex, as a CD13 inhibitor, reverses GC drug resistance and the underlying mechanism remain unclear. Methods: Herein, resistance to 5-fluorouracil (5-FU) was reversed in GC by ubenimex, and the underlying mechanism was determined using Cell Counting Kit-8 (CCK-8) assays, gene chip analysis, high content screening (HCS), transmission electron microscopy, flow cytometry, immunofluorescence and western blot assays. Results: Flow cytometry, transmission electron microscopy and immunofluorescence analyses indicated that ubenimex, an inhibitor of CD13, regulated the autophagy and apoptosis of SGC7901/5-FU cells by downregulating CD13 expression. In addition, Gene chip analysis and HCS demonstrated that epithelial membrane protein 3 (EMP3)/focal adhesion kinase (FAK) was a putative signalling pathway downstream of CD13. Furthermore, western blot analyses showed that ubenimex not only inhibited EMP3, FAK and nuclear factor-κB (NF-κB) expression but also suppressed GC autophagy and activated apoptosis by targeting CD13. These findings indicated a potential mechanism via the CD13/EMP3/FAK/NF-κB pathway and that the activity of which was restrained. Conclusions: Ubenimex affects autophagy and apoptosis to reverse GC cell resistance by targeting the CD13/EMP3/FAK/NF-κB pathway. These results showed that ubenimex is a promising agent that may inhibit GC autophagy to improve chemotherapeutic drug sensitivity and thereby reverse drug resistance.

Salvianolic acid A promotes mitochondrial biogenesis and mitochondrial function in 3T3-L1 adipocytes through regulation of the AMPK-PGC1α signalling pathway.

Mitochondrial dysfunction is associated with insulin resistance and type 2 diabetes (T2DM). Decreased mitochondrial abundance and function were found in white adipose tissue (WAT) of T2DM patients. Therefore, promoting WAT mitochondrial biogenesis and improving adipocyte metabolism may be strategies to prevent and reverse T2DM. Salvianolic acid A (SAA) has been found to exert anti-diabetic and lipid disorder-improving effects. However whether SAA benefits mitochondrial biogenesis and function in adipose tissue is unclear. Here, we evaluated SAA's effect on mitochondrial biogenesis and function in 3T3-L1 adipocytes and investigated its potential regulatory mechanism. Results showed that SAA treatment significantly promoted the transcription and expression of peroxisome proliferator-activated receptor γ coactivator- 1α (PGC-1α), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM). Meanwhile, SAA treatment significantly promoted mitochondrial biogenesis by increasing mitochondrial DNA (mtDNA) quantity, mitochondrial mass, and expression of mitochondrial respiratory chain enzyme complexes III and complex IV. These enhancements were accompanied by enhanced phosphorylation of AMPK and ACC and were suppressed by Compound C, a specific AMPK inhibitor. Furthermore, SAA treatment improved adipocytes mitochondrial respiration and stimulated ATP generation. These findings indicate that SAA exerts a potential therapeutic capacity against adipocytes mitochondrial dysfunction in diabetes by activating the AMPK-PGC-1α pathway.

Risk Factors for Chemotherapy-Induced Peripheral Neuropathy Caused by Nanoparticle Albumin-Bound Paclitaxel in Advanced Breast Cancer.

Breast cancer (BC) is one of the most common malignancies affecting women and the leading cause of related mortality worldwide. An estimated 2260000 new cases of BC were diagnosed in 2020, which have seriously threatened the health. Paclitaxel (PTX), a natural product isolated from the bark of the pacific yew, has been found to be effective in treating advanced BC. Chemotherapy-induced peripheral neuropathy (CIPN), which refers to the damage to the peripheral nerves caused by exposure to a neurotoxic chemotherapeutic agent, is a common side effect affecting the patients undergoing PTX chemotherapy. Significant research efforts are needed to identify the various risk factors associated with CIPN. Here, a univariate analysis in BC patients with nanonab-PTX treatment was performed. The rate of CIPN in BC patients with albumin-bound paclitaxel (nab-PTX) for more than four weeks was significantly higher than that of patients with chemotherapy for less than four weeks. Moreover, the rate of CIPN in BC patients receiving nab-PTX first-line chemotherapy was remarkably higher than that in BC patients receiving paclitaxel as a sequence scheme. Taken together, chemotherapy cycles and the priority of nab-PTX-based chemotherapy can be considered the potential risk factors for CIPN induced by nab-PTX.

Anti-inflammatory Mechanism of Action of Benzoylmesaconine in Lipopolysaccharide-Stimulated RAW264.7 Cells.

Background: Benzoylmesaconine (BMA), the most abundant monoester alkaloid in Aconitum plants, has some biological activities and is a potential therapeutic agent for inflammation-related diseases. However, the potential anti-inflammatory mechanisms of BMA have not been clarified. Purpose: This study aimed to investigate the underlying molecular mechanisms of the anti-inflammatory action of this compound using lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Methods: The release of pro-inflammatory cytokines and mediators were detected by nitric oxide (NO) assays, reactive oxygen species (ROS) assays, and enzyme-linked immunosorbent assays (ELISA) in LPS-activated RAW264.7 macrophage cells. Quantitative real-time PCR was used to measure the gene expression of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Cell viability was determined using a cell counting kit-8 (CCK-8) assay. The expression of iNOS, COX-2, mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB)-related proteins were detected by western blot, and nuclear translocation of p65 was observed by immunofluorescence. Results: BMA significantly decreased the production of IL-1ß, IL-6, TNF-α, PGE2, NO, and ROS and inhibited the protein and mRNA levels of COX-2 and iNOS in LPS-activated RAW264.7 macrophages. Moreover, LPS-induced phosphorylation of IκBα, JNK, p38, and ERK; degradation of IκBα; and nuclear translocation of p65 were significantly suppressed by BMA treatment. Conclusion: These findings demonstrate that the anti-inflammatory effect of BMA was through the suppression of the NF-κB and MAPK signaling pathways and that it may be a therapeutic agent targeting specific signal transduction events required for inflammation-related diseases.

SLC6A14 Depletion Contributes to Amino Acid Starvation to Suppress EMT-Induced Metastasis in Gastric Cancer by Perturbing the PI3K/AKT/mTORC1 Pathway.

Metastasis is the main obstacle for the treatment of gastric cancer (GC), leading to low survival rate and adverse outcomes in CG patients. SLC6A14, a general amino acid transporter, can import all the essential amino acids in a manner dependent on the NaCl-generated osmotic gradients. Herein, we constructed GC cell sublines with high (SGC7901-M and MKN28-M) and low (MKN28-NM and SGC7901-NM) metastatic ability. Putative functional genes advancing GC metastasis were identified using mRNA microarray analysis and High-Content Screening. In particular, most significant change with a dampening trend in the migration potentiality of GC cells emerged after SLC6A14 gene was silenced. SLC6A14 expression was positively correlated with the migrated capability of different GC cell lines, and SLC6A14 was also constitutively expressed in GC patients with venous or lymphatic invasion, lymph node, or distant metastasis and poor prognosis, thus prompting SLC6A14 as a nonnegligible presence in supporting GC migration and invasion. Consistently, SLC6A14 depletion drastically depressed GC metastasis in vitro and in vivo. Most importantly, pharmacological blockade and gene silence of SLC6A14 both restricted epithelial-mesenchymal transition- (EMT-) driven GC metastasis, in which attenuated activation of the PI3K/AKT/mTORC1 pathway caused by amino acid starvation was involved. In summary, it is conceivable that targeting SLC6A14 has a tremendous promising for the treatment of metastatic GC.

Malus toringoides (Rehd.) Hughes improves glucose and lipid metabolism and liver injury in high fructose-induced mice.

Malus toringoides (Rehd.) Hughes, as a traditional medicinal and edible plant used in Tibet, China, is used to treat hypertension, hyperlipidemia, and liver diseases. In recent decades, excessive fructose intake with diet has greatly increased the occurrence of a series of metabolic diseases including obesity, insulin resistance, hypertension, and hyperlipidemia. The present study was designed to investigate the effects of an ethanol extract of M. toringoides (EMT) on glucose and lipid metabolism and liver injury in high fructose-induced mice. The C57BL/6J male mice were orally administrated with 30% fructose solution for 8 weeks, and EMT was given orally for another 8 weeks. The level of liver lipids related parameters, hepatic oxidative stress, and inflammatory mediators was detected by the kits. The improving effects of EMT on liver injury and lipid accumulation of mice were observed by hematoxylin and eosin staining and Oil Red O staining. In vitro, the hypolipidemic effect of EMT on palmitic acid-induced HepG2 cells was detected by the kits and Oil Red O staining. Our results showed that EMT has the hypolipidemic effect in vivo and in vitro, and can improve liver injury caused by fructose intake though ameliorating oxidative stress and inflammatory responses. Thus, we suggested that EMT may be a candidate therapeutic agent to improve a series of metabolic diseases including obesity, insulin resistance, and hyperlipidemia. PRACTICAL APPLICATIONS: Our study was aimed to find a novel candidate drug for liver diseases using natural products. We assessed the protective effects of Malus toringoides (Rehd.) Hughes in the pathogenesis of glucose and lipid metabolism. In vivo, the plant significantly improved the disorder of blood lipid and blood glucose, and liver injury in mice induced by fructose, and in vitro, this plant significantly improved the lipid accumulation of HepG2 cells induced by palmitic acid. To sum up, our studies suggested that the plant may be beneficial in the prevention and management of diet-induced abnormal glucose and lipid metabolism and liver diseases. Therefore, it will be a candidate therapeutic agent to improve liver diseases.

The Single-Cell Sequencing: A Dazzling Light Shining on the Dark Corner of Cancer.

Tumorigenesis refers to the process of clonal dysplasia that occurs due to the collapse of normal growth regulation in cells caused by the action of various carcinogenic factors. These "successful" tumor cells pass on the genetic templates to their generations in evolutionary terms, but they also constantly adapt to ever-changing host environments. A unique peculiarity known as intratumor heterogeneity (ITH) is extensively involved in tumor development, metastasis, chemoresistance, and immune escape. An understanding of ITH is urgently required to identify the diversity and complexity of the tumor microenvironment (TME), but achieving this understanding has been a challenge. Single-cell sequencing (SCS) is a powerful tool that can gauge the distribution of genomic sequences in a single cell and the genetic variability among tumor cells, which can improve the understanding of ITH. SCS provides fundamental ideas about existing diversity in specific TMEs, thus improving cancer diagnosis and prognosis prediction, as well as improving the monitoring of therapeutic response. Herein, we will discuss advances in SCS and review SCS application in tumors based on current evidence.

Prediction of Unbound Vancomycin Levels in Intensive Care Unit and Nonintensive Care Unit Patients: Total Bilirubin May Play an Important Role.

BACKGROUND: The mean unbound vancomycin fraction and whether the unbound vancomycin level could be predicted from the total vancomycin level are still controversial, especially for patients in different groups, such as intensive care unit (ICU) versus non-ICU patients. Other relevant potential patient characteristics that may predict unbound vancomycin levels have yet to be clearly determined. METHODS: We enrolled a relatively large study population and included widely comprehensive potential covariates to evaluate the unbound vancomycin fractions in a cohort of ICU (n=117 samples) and non-ICU patients (n=73 samples) by using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. RESULTS: The mean unbound vancomycin fraction was 45.80% ± 18.69% (median, 46.01%; range: 2.13-99.45%) in the samples from the total population. No significant differences in the unbound vancomycin fraction were found between the ICU patients and the non-ICU patients (P=0.359). A significant correlation was established between the unbound and total vancomycin levels. The unbound vancomycin level can be predicted with the following equations: unbound vancomycin level=0.395×total vancomycin level+0.019×total bilirubin level+0.468 (R2=0.771) for the ICU patients and unbound vancomycin level=0.526×total vancomycin level-0.527 (R2=0.749) for the non-ICU patients. Overall, the observed-versus-predicted plots were acceptable. CONCLUSION: A significant correlation between the total and unbound vancomycin levels was found, and measurement of the unbound vancomycin level seems to have no added value over measurement of the total vancomycin level. The study developed parsimonious equations for predicting the unbound vancomycin level and provides a reference for clinicians to predict the unbound vancomycin level in adult populations.

Benzoylaconine Modulates LPS-Induced Responses Through Inhibition of Toll-Like Receptor-Mediated NF-κB and MAPK Signaling in RAW264.7 Cells.

Previous studies have shown that benzoylaconine (BAC), a representative monoester alkaloid, has a potential anti-inflammatory effect. This study investigated the underlying molecular mechanisms using the mode of LPS-activated RAW264.7 macrophage cells. Our findings showed that BAC significantly suppressed the release of pro-inflammatory cytokines and mediators, including IL-6, TNF-α, IL-1ß, ROS, NO, and PGE2. BAC treatment also effectively downregulated the elevated protein levels of iNOS and COX-2 induced by LPS in a dose-dependent manner. In this study, we found that BAC inhibited LPS-induced NF-κB activation by reducing the phosphorylation and degradation of IκBα by western blotting and blocking the nuclear translocation of p65 using an immunofluorescence assay. The elevated protein levels of JNK, p38, and ERK phosphorylation after LPS stimulation were restored effectively by BAC treatment. The protein expression of Toll-like receptor 4 (TLR4) and LPS-induced phosphorylation of TAK1, which is a crucial upstream regulatory factor of TLR-induced MAPK and NF-κB signaling, were inhibited by BAC in activated RAW264.7 macrophages. Moreover, BAC decreased the levels of TAK1 phosphorylation and pro-inflammatory cytokines and mediators associated with MAPK and NF-κB activation, similar to TLR4 inhibitor TAK-242. These findings demonstrated that BAC exhibited an anti-inflammatory effect by the inhibition of TLR-induced MAPK and NF-κB pathways, indicating that it could potentially be used for treating inflammatory diseases.

Ubenimex Suppresses the Ability of Migration and Invasion in Gastric Cancer Cells by Alleviating the Activity of the CD13/NAB1/MAPK Pathway.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors in China. Most GC patients are diagnosed at an advanced stage, for that the prognosis is dismal and metastasis is common. Although there have been increasing numbers of studies indicating that Ubenimex can suppress metastasis in GC, the underlying mechanism is still unknown. METHODS: Herein, the inhibitory effect of Ubenimex on GC metastasis, in which the underlining mechanism was determined using Gene chip analysis, high content screening (HCS), transwell assays, wound healing assays and Western blot assays. RESULTS: The results obtained from wound healing assays and transwell assays indicated that Ubenimex, an inhibitor of CD13, suppressed the migration and invasion of MKN-28, MGC-803, BGC-823 and SGC-790 cells, by downregulating CD13 expression. In addition, the findings acquired from Gene chip analysis and HCS demonstrated that NGFI-A-binding protein 1 (NAB1) was a putative target downstream of CD13. Furthermore, the results obtained from Western blot assays showed that Ubenimex not only inhibits NAB1 expression by targeting CD13, but also inhibits GC metastasis by mitigating the activity of the MAPK signaling pathway. These findings indicated a possible mechanism via the CD13/NAB1/MAPK pathway of which activity was restrained. CONCLUSION: Ubenimex exert the inhibitory effect on GC metastasis by targeting CD13, in which NAB1 expression and the activation of MAPK signaling pathway were both suppressed. This study identified a promising target for the inhibition of GC metastasis.

Facing coronavirus disease 2019: What do we know so far? (Review).

Although the World Health Organization declared the outbreak of coronavirus disease 2019 (COVID-19), which originated in China, as a public health emergency of international concern as early as January 30, 2020, the current COVID-19 epidemic is spreading rapidly. As of April 19, 2020, total of 2,392,165 confirmed cases had been reported in 211 countries and regions, with 614,421 (25.68%) cured cases and 164,391 (6.87%) deaths. Scientists and clinicians have made great efforts to learn much about COVID-19 so that it can be controlled as soon as possible. Herein, this review will discuss the epidemiology, pathology, clinical features, diagnosis and treatment of COVID-19 based on the current evidence.

Facing Cell Autophagy in Gastric Cancer - What Do We Know so Far?

Autophagy is a process by which misfolded proteins and damaged organelles in the lysosomes of tumor cells were degraded reusing decomposed substances and avoiding accumulation of large amounts of harmful substances. Here, the role of autophagy in the development of malignant transformation of gastric tumors, and the underlying mechanisms involved in autophagy formation, and the application of targeted autophagy in the treatment of gastric cancer were summarized.

CD13: A Key Player in Multidrug Resistance in Cancer Chemotherapy.

Cancer is one of the most serious diseases that are harmful to human health. Systemic chemotherapy is an optimal therapeutic strategy for the treatment of cancer, but great difficulty has been encountered in its administration in the form of multidrug resistance (MDR). As an enzyme on the outer cell surface, CD13 is documented to be involved in the MDR development of tumor cells. In this review, we will focus on the role of CD13 in MDR generation based on the current evidence.