Amphibian pore-forming protein ßγ-CAT drives extracellular nutrient scavenging under cell nutrient deficiency.

Nutrient acquisition is essential for animal cells. ßγ-CAT is a pore-forming protein (PFP) and trefoil factor complex assembled under tight regulation identified in toad Bombina maxima. Here, we reported that B. maxima cells secreted ßγ-CAT under glucose, glutamine, and pyruvate deficiency to scavenge extracellular proteins for their nutrient supply and survival. AMPK signaling positively regulated the expression and secretion of ßγ-CAT. The PFP complex selectively bound extracellular proteins and promoted proteins uptake through endolysosomal pathways. Elevated intracellular amino acids, enhanced ATP production, and eventually prolonged cell survival were observed in the presence of ßγ-CAT and extracellular proteins. Liposome assays indicated that high concentration of ATP negatively regulated the opening of ßγ-CAT channels. Collectively, these results uncovered that ßγ-CAT is an essential element in cell nutrient scavenging under cell nutrient deficiency by driving vesicular uptake of extracellular proteins, providing a new paradigm for PFPs in cell nutrient acquisition and metabolic flexibility.

Pore-forming protein ßγ-CAT promptly responses to fasting with capacity to deliver macromolecular nutrients.

During animal fasting, the nutrient supply and metabolism switch from carbohydrates to a new reliance on the catabolism of energy-dense lipid stores. Assembled under tight regulation, ßγ-CAT (a complex of non-lens ßγ-crystallin and trefoil factor) is a pore-forming protein and trefoil factor complex identified in toad Bombina maxima. Here, we determined that this protein complex is a constitutive component in toad blood, that actively responds to the animal fasting. The protein complex was able to promote cellular albumin and albumin-bound fatty acid (FA) uptake in a variety of epithelial and endothelial cells, and the effects were attenuated by a macropinocytosis inhibitor. Endothelial cell-derived exosomes containing largely enriched albumin and FAs, called nutrisomes, were released in the presence of ßγ-CAT. These specific nutrient vesicles were readily taken up by starved myoblast cells to support their survival. The results uncovered that pore-forming protein ßγ-CAT is a fasting responsive element able to drive cell vesicular import and export of macromolecular nutrients.

A pore-forming protein drives macropinocytosis to facilitate toad water maintaining.

Maintaining water balance is a real challenge for amphibians in terrestrial environments. Our previous studies with toad Bombina maxima discovered a pore-forming protein and trefoil factor complex ßγ-CAT, which is assembled under tight regulation depending on environmental cues. Here we report an unexpected role for ßγ-CAT in toad water maintaining. Deletion of toad skin secretions, in which ßγ-CAT is a major component, increased animal mortality under hypertonic stress. ßγ-CAT was constitutively expressed in toad osmoregulatory organs, which was inducible under the variation of osmotic conditions. The protein induced and participated in macropinocytosis in vivo and in vitro. During extracellular hyperosmosis, ßγ-CAT stimulated macropinocytosis to facilitate water import and enhanced exosomes release, which simultaneously regulated aquaporins distribution. Collectively, these findings uncovered that besides membrane integrated aquaporin, a secretory pore-forming protein can facilitate toad water maintaining via macropinocytosis induction and exocytosis modulation, especially in responses to osmotic stress.

Anti-N-methyl-D-aspartate-receptor antibody encephalitis combined with syphilis: A case report.

BACKGROUND: Anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis is a common type of autoimmune encephalitis characterized by complex clinical signs and variable imaging manifestations. The pathogenesis of the disease is unclear. Syphilis is an infectious disease caused by Treponema pallidum that can invade the nervous and immune systems and cause systemic symptoms. There are few reports of anti-NMDAR encephalitis with syphilis, and the association between them is unknown; both diseases are related to immune system damage. We report a case of anti-NMDAR encephalitis with syphilis. CASE SUMMARY: A 32-year-old man was admitted to our hospital with complaints of cognitive decline, diplopia, and walking instability during the previous 6 mo. He developed dysarthria, difficulty swallowing, and involuntary shaking of his head, neck, and limbs during the month prior to presentation. Cranial magnetic resonance imaging showed symmetrical abnormal signals in the pons, midbrain, and bilateral basal ganglia, and inflammatory demyelination was considered. The diagnosis of syphilis was confirmed based on the syphilis diagnosis test and the syphilis rapid test. He was given anti-syphilis treatment, but the above symptoms gradually worsened. Anti-NMDAR antibody was positive in cerebrospinal fluid but was negative in serum. Due to the cerebrospinal fluid findings, anti-NMDAR encephalitis was a consideration. According to the patient's weight, he was treated with intravenous methylprednisolone 1 g QD for 5 d, with the dose gradually decreased for 6 mo, and immunoglobulin 25 g QD for 5 d; his symptoms improved after treatment. CONCLUSION: This case shows that anti-NMDAR encephalitis may be combined with syphilis, which should be recognized to avoid misdiagnosis and treatment delay.

The rs75932628 and rs2234253 polymorphisms of the TREM2 gene were associated with susceptibility to frontotemporal lobar degeneration in Caucasian populations.

Polymorphisms of the triggering receptor expressed on myeloid cells 2 (TREM2) gene have been reported to be potentially associated with the risks of developing frontotemporal lobar degeneration (FTLD), with inconsistent conclusions. This study aims to comprehensively investigate the potential role of TREM2 variants in FTLD risks via a meta-analysis. We included a total of eight eligible articles. For TREM2 rs75932628, we observed a significantly increased FTLD risk in the models of T vs. C [Association Test, odds ratio (OR) = 2.43, 95% confidence interval (CI) = 1.43∼4.14, P = 0.001], CT vs. CC (OR = 2.27, 95% CI = 1.39∼3.71, P = 0.001), CT + TT vs. CC (OR = 2.27, 95% CI = 1.38∼3.71, P = 0.001), and Carrier T vs. C (OR = 2.26, 95% CI = 1.38∼3.69, P = 0.001). Similarly, we observed positive results for TREM2 rs2234253 in all of the genetic models (all OR > 1, P = 0.030). Nevertheless, we did not observe any statistical difference between the case and control groups in the pooled analyses of TREM2 rs142232675 and rs143332484 (all P > 0.05). Our findings identified the rs75932628 and rs2234253 polymorphisms of the TREM2 gene as risk factors for FTLD in Caucasian populations.

Updated meta-analysis of the role of APOE ε2/ε3/ε4 alleles in frontotemporal lobar degeneration.

We performed an updated meta-analysis to assess the role of the ε2/ε3/ε4 alleles of Apolipoprotein E gene (APOE) in frontotemporal lobar degeneration (FTLD). The relevant articles were retrieved from PubMed, CENTRAL, EMBASE and Web of Science databases, and 51 eligible case-control studies with 5123 cases and 20566 controls were selected after screening according to inclusion and exclusion criteria. Our analysis demonstrated that APOE ε4 was associated with increased FTLD risk in all genetic models (ε4 vs. ε3 allele, ε4 vs. ε2 allele, ε4 vs. ε2+ε3+ε4 allele, ε4 vs. ε2+ε3+ε4 carrier, ε4ε4 vs. ε3ε3, ε3ε4 vs. ε3ε3, ε3ε4+ε4ε4 vs. ε3ε3, ε4ε4 vs. ε3ε3+ε3ε4, all P < 0.01, odds ratio [OR] > 1). Subgroup analysis revealed significant association between APOE ε4 and FTLD (P < 0.01, OR > 1) for the Caucasian, Italian, population based (PB), P > 0.05 value of the Hardy-Weinberg Equilibrium (HWE), Newcastle-Ottawa scale score > 6, and behavioral variant frontotemporal dementia (bvFTD) subgroups. However, there was no significant association between the APOE ε2 allele and FTLD (P > 0.05) in most genetic models and sub-group analyses. Begg's and Egger's tests also revealed no publication bias, and sensitivity analysis showed that our data analysis was robust. Thus our meta-analyses suggest that APOE ε4 is a genetic risk factor in patients with FTLD.

[Levels of polychlorinated biphenyls in adolescents' hair from Gongzhuling, Jilin].

Adolescents' (12-18) hair samples (n = 23) collected from Gongzhuling Jilin were analyzed for 30 polychlorinated biphenyl (PCB) congeners by gas chromatograph-mass spectrometer (GC-MS). The distribution characteristics, sources and relationship with genders of PCBs in adolescents' hair were addressed as well. The results indicated that the detection frequency of PCBs were 100% with average concentration of (68.85 +/- 36.72) ng x g(-1) and detection range from 11.66 ng x g(-1) to 127.86 ng x g(-1), respectively. This region was contaminated to some extent. CB-28, CB-52, CB-87 and CB-82 were the major congeners which occupied 62%. Penta-CBs were the dominant contributors (39%), followed by tetra-CBs (29%) and tri-CBs (18%). The different distributions of PCBs congeners in hair from other human tissues and the air are believed to be the fact that PCBs in human hair not only came from endogenous dietary uptake of the contaminants, but also from exogenous atmospheric deposition. The results clearly indicated that these pollutants mainly came from industrial pollution. When gender was considered, significantly higher concentrations for most of the investigated contaminants were found in female compared with male.

Biotin-avidin amplified enzyme-linked immunosorbent assay for determination of isoflavone daidzein.

A biotin-avidin amplified enzyme-linked immunosorbent assay (BA-ELISA) method was developed and optimized for the determination of a weakly estrogenic isoflavone daidzein in serum, urine and Puerariae radix. Specific polyclonal antibody was produced against daidzein by immunization of rabbits with a conjugate of 7-O-(carboxymethyl)-daidzein and bovine serum albumin (BSA). The polyclonal antibody showed specific recognition of daidzein, while cross-reactivities to coumarin, 4-hydroxycoumarin, phenol, and other isoflavones such as puerarin and rutin were all lower than 1%. The linear range of daidzein calibration curve was 0.1-1000ngmL(-1). The detection limit was found to be 0.04ngmL(-1), and the intra-assay and inter-assay coefficients of variation were 7 and 16%, respectively. Human serum and urine samples were spiked with known amounts of daidzein and measured by the established BA-ELISA. Recoveries were between 91 and 107%. Daidzein in P. radix was determined by the BA-ELISA method and HPLC method, and the content of daidzein was determined to be 0.0219 and 0.0194%, respectively. The results indicated that there was a good agreement between the two methods. The established method is very useful for monitoring daidzein in biological samples and traditional Chinese medicine.

[Relationship between juxtapapillary duodenal diverticula and biliopancreatic diseases in patients over 60 years old].

OBJECTIVE: To explore the relationship between juxtapapillary duodenal diverticula and biliopancreatic diseases in the > 60-year-old patients. METHODS: A total of 102 patients over 60 years of age with juxtapapillary duodenal diverticula were definitely diagnosed by endoscopic retrograde cholangio-pancreatography (ERCP), all of whom also had biliopancreatic diseases as confirmed by B ultrasound and/or CT scan. RESULTS: Of all the patients, 75 were identified as having biliary calculi (73.53%), and 21 had pancreatitis (20.6%). Among the 54 patients undergoing cholecystectomy, 29 (85.29%) developed common bile duct calculi postoperatively. CONCLUSIONS: Juxtapapillary duodenal diverticula in senior patients is often associated with biliopancreatic diseases, and is particularly in close relation to common bile duct calculi secondary to biliary calculi and cholecystectomy.