Metabolite secretions of Lactobacillus plantarum YYC-3 may inhibit colon cancer cell metastasis by suppressing the VEGF-MMP2/9 signaling pathway.

BACKGROUND: Colorectal cancer (CRC) is a major clinical challenge, and the gut microbiome plays important roles in the occurrence and metastasis of CRC. Lactobacillus and their metabolites are thought to be able to suppress the growth of CRC cells. However, the antimetastatic mechanism of Lactobacillus or their metabolites toward CRC cells is not clear. Therefore, the aim of this study was to assess the inhibitory mechanism of cell-free supernatants (CFSs) of L. rhamnosus GG, L. casei M3, and L. plantarum YYC-3 on metastasis of CRC cells. RESULTS: YYC-3 CFS showed the highest inhibitory effect on CRC cell growth, invasion and migration, and inhibited MMP2, MMP9, and VEGFA gene and protein expression, and protein secretion. Furthermore, it suppressed the activities of MMPs by gelatin zymography. Moreover, the effective compounds in these CFSs were analyzed by Q Exactive Focus liquid chromatography-mass spectrometry. CONCLUSIONS: Our results showed that metabolite secretions of YYC-3 may inhibited cell metastasis by downregulating the VEGF/MMPs signaling pathway. These data suggest that treatment of CRC cells with metabolites from L. plantarum YYC-3 may reduce colon cancer metastasis.

Utilization of Microdissected Thin Perforator Flap Technique in the Treatment of Bulky and Deformed Skin Flaps.

BACKGROUND: This study investigates the feasibility and clinical impact of the microdissected thin perforator skin flap strategy on bulky and deformed skin flaps during second-stage revision surgery. METHODS: Seventeen patients were selected and underwent the microdissected thin perforator skin flap technique to treat bulky and deformed skin flaps after free flap reconstruction between October 2013 and October 2015. Perforator vessels were isolated and protected under a microscope. Subdermal fat with a thickness of 4 mm to 7 mm was preserved, and excess adipose tissue was resected. RESULTS: No skin flap necrosis was observed after the operation in all 17 patients, and all wounds healed without complications. Patients were followed up for 3 to 24 months, with an average follow-up time of 10 months. The skin flaps maintain normal color and texture. Both appearance and function of the recipient sites were improved significantly. CONCLUSIONS: The utilization of microdissected thin perforator flap technique to further thin bulky skin flaps at the second stage can be effective in a single operation. The blood supply of all free flaps was preserved, with no evidence of necrosis or healing complications. This technique offers an effective approach for secondary thinning of bulky free flaps.

Generation and characterization of dipeptidyl peptidase-IV inhibitory peptides from trypsin-hydrolyzed α-lactalbumin-rich whey proteins.

Dipeptidyl peptidase-IV (DPP-IV) is an enzyme that break down the antidiabetic hormone glucagon-like peptide-1. Therefore, inhibition of DPP-IV could be an effective strategy to treat Type 2 diabetes (T2D). The α-lactalbumin-rich whey protein concentrate was hydrolyzed by trypsin, and the hydrolysates were then fractionated at a semi-preparative scale using a Superdex Gel filtration Chromatography. The peptides were analyzed by using HPLC coupled with tandem mass spectrometry (RP-HPLC-MS/MS), and their Dipeptidyl peptidase-IV inhibitory activity was determined by the enzymatic assay. Among tested fragments, a potent fragment (LDQWLCEKL), with the half-maximal inhibitory concentration (IC50) of 131 µM was obtained. Further analysis shows that the LDQWLCEKL peptide corresponds to the amino acid sequence of f(115-123) in α-lactalbumin. Furthermore, LDQWLCEKL exhibited a typical non-competitive mode of inhibition. The results indicate that α-lactalbumin contains active peptides with DPP-IV inhibitory activity that may be used to prevent and treat T2D.

Novel Compound Heterozygous DST Variants Causing Hereditary Sensory and Autonomic Neuropathies VI in Twins of a Chinese Family.

Background: Hereditary sensory and autonomic neuropathies (HSANs) are a rare and severe group of sensory axonal neuropathies. HSANs have been classified into eight groups based on mode of inheritance, clinical features, and the involved genes. HSAN-VI, perhaps the most notable type, is an autosomal recessive disease, which manifests as the severely impaired pain sensitivity, autonomic disturbances, distal myopathy, spontaneous or surgical amputations, and sometimes early death. Mutations in DST have been identified as the cause of HSAN-VI. DST encodes dystonin, a member of the plakin protein family that is involved in cytoskeletal filament networks. Dystonin has seven major isoforms in nerve, muscle, and epithelium. Material and Methods: The present study investigated a Chinese family with HSAN and explored potential pathogenic variants using whole-exome sequencing (WES). Variants were screened and filtered through bioinformatics analysis and prediction of variant pathogenicity. Co-segregation analysis was subsequently conducted. Results: We identified compound heterozygous variants of DST (c.3304G>A, p.V1102I and c.13796G>A, p.R4599H) in two patients. Conclusion: We reported on a Chinese family with HSAN-VI family and detected the disease-causing variants. Our description expands the spectrum of known DST variants and contributes to the clinical diagnosis of HSAN-VI.

Reconstructive surgery for foot and ankle defects in pediatric patients: Comparison between anterolateral thigh perforator flaps and deep inferior epigastric perforator flaps.

BACKGROUNDS: Due to the delicate tissue, small blood vessels and incomplete development of interarticular ligaments, skin and soft-tissue defects of the foot and ankle in pediatric patients remain a challenge for orthopedic and plastic surgeons. Anterolateral thigh perforator (ALTP) flap and deep inferior epigastric perforator (DIEP) flap are the most commonly used flaps for the repair of lower-extremity soft-tissue defects. The literature contains a shortage of evidence involving the differences between ALTP and DIEP flaps in the reconstruction of young patients with complex foot and ankle defects. This study was designed to determine which type of flap is better for foot and ankle repair in pediatric patients. METHODS: From January 2004 to January 2018, 79 children younger than 14 years treated with DIEP flap (41 cases) or ALTP flap (38 cases) for composite defects of the feet and ankles were retrospectively investigated. The two groups were homogeneous in terms of age, the location of the defect, etiology, and flap area. Complications, scarring, cosmetic appearance, flap sensory recovery, and functional outcome were analyzed, and statistical analysis was performed. RESULTS: The ALTP group had shorter operation time (155.0 ±â€¯12.0 min vs 212.2 ±â€¯23.9 min), flap harvested time (39.6 ±â€¯5.1 min vs 57.2 ±â€¯10.4 min), and operative blood loss (143.4 ±â€¯23.7 ml vs 170.7 ±â€¯44.7 ml) than the DIEP group (P <  0.05). In short-term follow-up, ALTP group showed a lower flap necrosis rate (5.3% vs 24.4%) and vascular insufficiency rate (2.6% vs 19.5%) than DIEP group (P <  0.05). In long-term follow-up, ALTP group showed a lower late complication rate and better cosmetic, functional, scar outcomes than DIEP group (P <  0.05). CONCLUSIONS: The study showed that an ALTP flap may brings better results than a DIEP flap in terms of short- and long-term complications, scarring, and morpho-functional outcomes for pediatric patients undergoing reconstruction of foot and ankle defects.

Antidiabetic Effect of High-Chromium Yeast Against Type 2 Diabetic KK-Ay Mice.

High chromium yeast has attracted many researchers for its high efficiency and high safety among chromium supplements. The preventive effect of oral high-chromium yeast on diabetes was assessed using KK-AY mice. Sixteen-wk-old type 2 diabetic KK-AY mice were divided into five groups and orally administered with two types of drying processed high-chromium yeast, chromium picolinate at 1000 µg Cr/kg/d, metformin (positive control), and normal yeast (negative control) for 13 weeks. The spray-dried high-chromium yeast significantly delayed the onset of hyperglycemia in type 2 diabetic KK-AY mice (P < 0.05) and significantly improved fasting blood glucose, TG(triglyceride), and TCHO(total cholesterol) . Histopathological analysis showed that the spray-dried high-chromium yeast led to high affinities for the stains to the ß-cells in the islets of Langerhans and alleviated hepatic steatosis. High-chromium yeast could be a potential candidate for nutritional supplement to ameliorate diabetes. PRACTICAL APPLICATION: Chromium plays an important role in fat and carbohydrate metabolism. The result show that spray-dried high chromium yeast significantly delayed the onset of hyperglycemia in type 2 diabetic KK-AY mice. As one of chromium supplements, the purpose of this study is to examine the efficacy of high chromium yeast on the type 2 diabetes and drying method on its bioactivity, which will be useful for research and development of high-chromium yeast and improvement of pharmacological activity-based quality control.

Gene knockout and overexpression analysis revealed the role of N-acetylmuramidase in autolysis of Lactobacillus delbrueckii subsp. bulgaricus ljj-6.

Autolysis of lactic acid bacteria (LAB) plays a vital role in dairy processing. During cheese making, autolysis of LAB affects cheese flavor development through release of intracellular enzymes and restricts the proliferation of cells in yogurt fermentation and probiotics production. In order to explore the mechanism of autolysis, the gene for the autolytic enzymes of L. bulgaricus, N-acetylmuramidase (mur), was cloned and sequenced (GenBank accession number: KF157911). Mur gene overexpression and gene knockout vectors were constructed based on pMG76e and pUC19 vectors. Recombinant plasmids were transformed into L. bulgaricus ljj-6 by electroporation, then three engineered strains with pMG76e-mur vector and fifteen engineered strains with pUC19-mur::EryBII were screened. The autolysis of the mur knockout strain was significantly lower and autolysis of the mur overexpressed strain was significantly higher compared with that of the wild type strain ljj-6. This result suggested that the mur gene played an important role in autolysis of L. bulgaricus. On the other hand, autolytic activity in a low degree was still observed in the mur knockout strain, which implied that other enzymes but autolysin encoded by mur were also involved in autolysis of L. bulgaricus.

A practical therapeutic protocol for cervical tuberculosis.

PURPOSE: Cervical tuberculosis (CTB) is a relatively rare entity, even in endemic countries. Currently, management ranges from conservative to radical surgical approaches. We report our experience in diagnosing and treating 66 cases of CTB in the past eight years using our CTB therapeutic protocol. METHODS: All patients diagnosed with CTB were followed up over a 3.5-year period. Patients were divided into three grades using clinicoradiological criteria designed to evaluate the initial severity of the disease. Overall performance status was assessed based on the American Spinal Injury Association (ASIA) scale. Neurological recovery was evaluated with the ASIA scale as well as using X-rays and computed tomography every four weeks for the initial three months and every three months thereafter. RESULTS: The mean follow-up duration was 38.2 ± 6.2 months. No mortality occurred. One case of recurrence due to irregular antitubercular treatment (ATT) was cured by abscess clearing and regular ATT. All other patients had good clinicoradiological outcomes, regardless of grading. CONCLUSIONS: The use of our proposed scoring system and management protocol allowed speedy management of CTB.