Short-chain fatty acids: bridges between diet, gut microbiota, and health.

In recent years, gut microbiota has become a hot topic in the fields of medicine and life sciences. Short-chain fatty acids (SCFAs), the main metabolites of gut microbiota produced by microbial fermentation of dietary fiber, play a vital role in healthy and ill hosts. SCFAs regulate the process of metabolism, immune, and inflammation and have therapeutic effects on gastrointestinal and neurological disorders, as well as antitumor properties. This review summarized the production, distribution, and molecular mechanism of SCFAs, as well as their mechanisms of action in healthy and ill hosts. In addition, we also emphasized the negative effects of SCFAs, aiming to provide the public with a more comprehensive understanding of SCFAs.

Immune Checkpoint Neuropilins as Novel Biomarkers and Therapeutic Targets for Pancreatic Cancer.

The traditional immune checkpoint blockade therapy benefits some patients with cancer, but elicits no response in certain cancers, such as pancreatic adenocarcinoma (PAAD); thus, novel checkpoints and effective targets are required. Here, we found that there was a higher Neuropilin (NRP) expression in tumor tissues as novel immune checkpoints, which was associated with poor prognosis and pessimistic responses to immune checkpoint blockade therapy. In the tumor microenvironment of PAAD samples, NRPs were widely expressed in tumor, immune and stromal cells. The relationship of NRPs with tumor immunological features in PAAD and pan-cancer was evaluated using bioinformatics methods; it was positively correlated with the infiltration of myeloid immune cells and the expression of most immune checkpoint genes. Bioinformatics analysis, in vitro and in vivo experiments suggested that NRPs exhibit potential immune-related and immune-independent pro-tumor effects. NRPs, especially NRP1, are attractive biomarkers and therapeutic targets for cancers, particularly PAAD.

Renal-hepatic-pancreatic dysplasia-1 with a novel NPHP3 genotype: a case report and review of the literature.

BACKGROUND: Renal-hepatic-pancreatic dysplasia type 1 (RHPD1) is a rare sporadic and autosomal recessive disorder with unknown incidence. RHPD1 is caused by biallelic pathogenic variants in NPHP3, which encode nephrocystin, an important component of the ciliary protein complex. CASE PRESENTATION: In this case report, we describe a male newborn who was confirmed by ultrasound to have renal enlargement with multiple cysts, pancreatic enlargement with cysts, and increased liver echogenicity, leading to the clinical diagnosis of RHPD. In addition, a compound heterozygous pathogenic variant, namely, NPHP3 c.1761G > A (p. W587*) and the c.69delC (p. Gly24Ala24*11) variant, was detected by WES. The patient was clinically and genetically diagnosed with RHPD1. At 34 h of life, the infant died of respiratory insufficiency. CONCLUSION: This is the first published case of RHPD1 in China. This study broadens the known range of RHPD1 due to NPHP3 pathogenic variants.

The Role and Mechanism of Autophagy in Pancreatic Cancer: An Update Review.

Pancreatic cancer, with high morbidity and mortality rates, is one of the most malignant tumors worldwide. Despite extensive research, the prognosis remains poor. Autophagy, a lysosomal-mediated, highly conserved degradation process that removes abnormal proteins and damaged organelles from the body, is upregulated in pancreatic ductal adenocarcinoma. Based on differences in the tumor microenvironment and tumor stage, the functions of autophagy in the pathophysiology and treatment of pancreatic cancer differ. In the initial phase, autophagy inhibits the transformation of precancerous lesions to cancer. However, in the progressive stage, autophagy promotes tumor growth. Autophagy is also one of the main mechanisms of drug resistance during treatment. Here, we describe the role of autophagy in pancreatic cancer progression and discuss relevant treatment strategies for this disease.

Granulocyte-macrophage colony-stimulating factor protects mice against hepatocellular carcinoma by ameliorating intestinal dysbiosis and attenuating inflammation.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. The gut microbiota can help maintain healthy metabolism and immunity. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a critical factor in promoting health and homeostasis; it promotes intestinal immunity, stimulates bone marrow precursors to generate macrophage colonies, and enhances the antibacterial and antitumor activity of circulating monocytes. As such, GM-CSF may protect against HCC development by regulating immunity as well as intestinal microecology. AIM: To investigate the impact of GM-CSF on the gut microbiome and metabolic characteristics of HCC. METHODS: Thirty-six male BALB/c nude mice were divided into three groups: Control (n = 10), HCC (n = 13), and HCC + GM-CSF (GM-CSF overexpression, n = 13). We utilized HCC cells to establish orthotopic transplantation tumor models of HCC with normal and over-expressing GM-CSF. Liver injury, immune inflammatory function and intestinal barrier function were evaluated. The fecal microbiome and metabolome were studied using 16S rRNA absolute quantification sequencing and gas chromatography-mass spectrometry. RESULTS: GM-CSF overexpression significantly affected the gut microbiome of mice with HCC and resulted in a high abundance of organisms of the genera Roseburia, Blautia and Butyricimonass, along with a significant reduction in Prevotella, Parabacteroides, Anaerotruncus, Streptococcus, Clostridium, and Mucispirillum. Likewise, GM-CSF overexpression resulted in a substantial increase in fecal biotin and oleic acid levels, along with a prominent decrease in the fecal succinic acid, adenosine, fumaric acid, lipoic acid, and maleic acid levels. Correlation analysis revealed that the intestinal microbiota and fecal metabolites induced by GM-CSF were primarily involved in pathways related to reducing the inflammatory response, biotin metabolism, and intestinal barrier dysfunction. CONCLUSION: GM-CSF can protect against HCC development by regulating immunity and modulating the abundance of specific intestinal microorganisms and their metabolites. This study provides new insights into the therapeutic approaches for HCC.

NRP1 is a Prognostic Factor and Promotes the Growth and Migration of Cells in Intrahepatic Cholangiocarcinoma.

BACKGROUND: Neuropilin-1 (NRP-1) participates in cancer cell proliferation and metastasis as a multifunctional co-receptor by interacting with multiple signaling pathways. However, few studies have addressed the precise function and prognosis analysis of NRP1 in intrahepatic cholangiocarcinoma (ICC). We aimed to study the correlations between NRP1 and clinicopathological characteristics and NRP1 effect on ICC cell line functions. METHODS: NRP1 mRNA and its protein levels in human ICC tissues and cell lines were detected by IHC, qRT-PCR, and WB method. Transwell, wound healing, and CCK-8 assays were performed to verify the effects of NRP1 knockdown and overexpression on cell migration and proliferation capability. RESULTS: NRP1 proteins and mRNA levels increased in ICC tissues compared to those in paired adjacent non-tumor tissues. High NRP1 expression of ICC tissues was related to poor prognosis. NRP1 expression level was expected to be an independent prognosticator for overall survival and cumulative tumor recurrence, and was closely related to tumor number (P=0.047). Knockdown of NRP1 inhibited cell proliferation and migration capability of RBE cells in vitro, and NRP1 overexpression in 9810 cells accelerated proliferation and migration. Additionally, NRP1 may promote cell proliferation and migration in ICC via the FAK/PI3-K/AKT pathway. CONCLUSION: As an oncogene, NRP1 may function as a candidate target and prognostic biomarker of value for ICC therapy.

Neuropilin1 silencing impairs the proliferation and migration of cells in pancreatic cancer.

BACKGROUND: Neuropilin1 (NRP1) participates in cancer cell proliferation, migration, and metastasis as a multifunctional co-receptor by interacting with multiple signal pathways, but few studies have addressed the precise function of NRP1 in pancreatic cancer (PACA) cells. We aimed to study whether NRP1 gene silencing involved in the proliferation and migration of PACA cells in vitro. METHODS: A lentiviral vector expressing NRP1 shRNA was constructed and transfected into human PACA cells (CFPAC-1 and PANC-1). The expression of NRP1 protein and mRNA was detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) assay, respectively. CCK-8 assay, wound healing assay, and transwell assay were conducted to examine the effect of NRP1 silencing on cells proliferation and migration capability. RESULTS: Results of qRT-PCR and Western blot showed successfully established, stably transfected shRNA-NRP1 cells in PACA cells. The proliferation capacity of PACA cells in NRP1 shRNA group was lower significantly than that in the negative control (NC) group (P < .05). The invasion and migration capability of PACA cells in NRP1 shRNA group was lower significantly than that in the NC group (P < .01). CONCLUSIONS: NRP1-shRNA lentiviral interference vectors can effectively decrease NRP1 gene expression in PACA cells, thereby inhibiting cells proliferation and migration, which provides a basis for finding a valuable therapeutic target for PACA therapy.

[Influence of fruit size of Camellia meiocarpa on growth of oil tea weevil, Curculio chinensis (Coleoptera: Curculionidae)].

The relationship between mature larval mass of oil tea weevil (Curculio chinensis) and fruit volume of its host plant oil tea (Camellia meiocarpa) was fitted with Logistic equation in order to understand the restriction of host fruit size on large larval growth and development of the weevil. The results showed that the larval mass increased with the increasing host fruit volume, which was in good conformity with the Logistic model. The weevil larval growth followed the principle of diminishing marginal utility, and it could be divided into two periods, the fast-growing period (<3.216 cm3, one larva per fruit; <4.747 cm3, two larvae per fruit ) and the asymptotic growing period (>3.216 cm3, one larva per fruit; >4.747 cm3, two larvae per fruit). The minimum fruit size threshold was 1500 cm3 for one larva per fruit, and 2.539 cm3 for two larvae per fruit. The temporal pattern that the mature larvae exited from their host fruits was established, the number of larvae escaping from their host fruits decreased daily after the fruit collection, and the larval escaping peak largely appeared from 6:00 to 10:00 AM with 43.9% of total escaping number, and especially from 7:00 to 8:00 AM with 21.1% of total escaping number. The bigger the larvae, the earlier exited from their host fruits. The restriction of fruit size on growth and development of oil tea weevil was observed, and it should be a behavioral adaptation strategy to increase the offspring' s fitness for the parental weevil adults to oviposit on the bigger fruits.

CHL1 is involved in human breast tumorigenesis and progression.

Neural cell adhesion molecules (CAM) play important roles in the development and regeneration of the nervous system. The L1 family of CAMs is comprised of L1, Close Homolog of L1 (CHL1, L1CAM2), NrCAM, and Neurofascin, which are structurally related trans-membrane proteins in vertebrates. Although the L1CAM has been demonstrated play important role in carcinogenesis and progression, the function of CHL1 in human breast cancer is limited. Here, we found that CHL1 is down-regulated in human breast cancer and related to lower grade. Furthermore, overexpression of CHL1 suppresses proliferation and invasion in MDA-MB-231 cells and knockdown of CHL1 expression results in increased proliferation and invasion in MCF7 cells in vitro. Finally, CHL1 deficiency promotes tumor formation in vivo. Our results may provide a strategy for blocking breast carcinogenesis and progression.

Molecular clone and expression of a NAD+-dependent glycerol-3-phosphate dehydrogenase isozyme gene from the halotolerant alga Dunaliella salina.

Glycerol is an important osmotically compatible solute in Dunaliella. Glycerol-3-phosphate dehydrogenase (G3PDH) is a key enzyme in the pathway of glycerol synthesis, which converts dihydroxyacetone phosphate (DHAP) to glycerol-3-phosphate. Generally, the glycerol-DHAP cycle pathway, which is driven by G3PDH, is considered as the rate-limiting enzyme to regulate the glycerol level under osmotic shocks. Considering the peculiarity in osmoregulation, the cDNA of a NAD(+)-dependent G3PDH was isolated from D. salina using RACE and RT-PCR approaches in this study. Results indicated that the length of the cDNA sequence of G3PDH was 2,100 bp encoding a 699 amino acid deduced polypeptide whose computational molecular weight was 76.6 kDa. Conserved domain analysis revealed that the G3PDH protein has two independent functional domains, SerB and G3PDH domains. It was predicted that the G3PDH was a nonsecretory protein and may be located in the chloroplast of D. salina. Phylogenetic analysis demonstrated that the D. salina G3PDH had a closer relationship with the G3PDHs from the Dunaliella genus than with those from other species. In addition, the cDNA was subsequently subcloned in the pET-32a(+) vector and was transformed into E. coli strain BL21 (DE3), a expression protein with 100 kDa was identified, which was consistent with the theoretical value.

[Establishment and primary application of sandwich ELISA method to detect tenascin-C].

AIM: To establish a sandwich method to detect tenascin-c on the basis of preparation of monoclonal antibodies (mAbs) against tenascin-C (TN-C). METHODS: The ascites of three stains of mAbs (No. 1A8, 3H7 and 4D6) were prepared and purified. The mAbs were conjugated with HRP and paired, respectively. The recombinant TN-C was taken as standard to analyze the optimal combination between mAbs. The sera TN-C concentrations of patients with osteosarocoma and the normal persons were evaluated with the sandwich ELISA method. RESULTS: Among these mAbs, the sensitivity was obtained when combined the coated 1A8 with HRP-4D6. The sera TN-C significantly higher than the normal controls. CONCLUSION: The sandwich ELISA method to detect TN-C was established successfully. The sera TN-C concentrations of patients with osteosarcoma and the normal persons were found distinct with the sandwich method.

[Docetaxel and capecitabine combination chemotherapy for patients with anthracycline-resistant metastatic breast cancer].

OBJECTIVE: To evaluate the efficacy and safety of docetaxel and capecitabine combination chemotherapy (DC regimen) for patients with anthracycline-resistant metastatic breast cancer. METHODS: Thirty-two patients with anthracycline-resistant metastatic breast cancer were treated with a docetaxel and capecitabine combination regimen. All patients received oral administration of capecitabine at a dose of 1250 mg/m(2) twice daily, within 30 min after meal on D1 to D14, and intravenous infusion of docetaxel at a dose of 75 mg/m(2) on D1. The regimen was repeated every 3 weeks. RESULTS: A total of 126 cycles of DC regimen were administered in the 32 cases, with a median of 4 cycles. The overall response rate was 46.9%. Among the 32 patients, there were complete response in 1, partial response in 14, stable disease in 11 and progressive disease in 6 cases. The median time to progression (TTP) was 5.6 months. The one-year survival rate was 56.3%. The effective cases in different metastatic organs were: 8 cases in the lung, 6 cases in the liver, 3 cases in the soft tissue and 3 cases in the lymph nodes. The common adverse reactions were myelosuppression, hand-foot syndrome, nausea and vomiting. Neutropenia was observed in 84.4% of the patients. Two patients developed degree IV myelosuppression. CONCLUSION: The combination chemotherapy regimen of docetaxel plus capecitabine is well-tolerated and effective for anthracycline-resistant metastatic breast cancer.

[Effect of levonorgestrel-releasing intrauterine system in the treatment of adenomyosis].

OBJECTIVE: To assess the clinical efficacy of levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of adenomyosis. METHODS: Forty-two patients with adenomyosis diagnosed by clinical symptoms, MRI, laparoscopy and/or chromatic colour type-B ultrasound were treated with LNG-IUS, and the menstrual blood volume, severity of dysmenorrhea and uterine volume were observed three months later. RESULTS: After 3 month treatment of LNG-IUS, the menstrual blood volume reduced significantly to (27 +/- 11)% of that before treatment. The uterine volume was decreased from (143 +/- 33) cm(3) to (115 +/- 22) cm(3) (P < 0.05). Dysmenorrhea was completely relieved or significantly alleviated. Hemoglobin recovered to (124 +/- 8) g/L (P < 0.05) in 20 patients with anemia. CONCLUSION: LNG-IUS is an effective and safe method in the short-term treatment of adenomyosis.