Research progress into the application of Mycobacterium phlei in veterinary medicine.

Mycobacterium phlei is a gram-positive acid-fast mycobacterium from the family Mycobacteriaceae. It is a valuable resource for both natural drugs and microecological preparations. It has been widely used in the field of human medicine; however, in the field of animal husbandry and veterinary medicine, the research and application of M. phlei is still in the preliminary exploration stage. This study aims to summarize the research progress of M. phlei in the field of veterinary medicine and provide a valuable reference for future research. Key words, such as 'M. phlei', 'veterinary field', 'immune balancer', 'genome' and other relevant words to this study, were used to search through PubMed, Web of Science, SciELO, Science Direct and Google Scholar databases. The results showed that the culture conditions of M. phlei were relatively simple, but its bacterial composition and genome sequence were relatively complex, and various components in the cell wall may have immunoregulatory effects. Therefore, the inactivated preparation made from M. phlei can have various applications in the veterinary field, such as growth regulation, immune regulation, antitumour, anti-parasite and asthma treatment. The literature review indicates that M. phlei preparation is an efficient and convenient immune system balance agent. Despite the challenges associated with the use of M. phlei preparations, it has a strong potential for application in veterinary medicine.

Limbal Niche Cells and Three-Dimensional Matrigel-Induced Dedifferentiation of Mature Corneal Epithelial Cells.

Purpose: To investigate the phenotypic changes of mature corneal epithelial cells (MCECs) that cocultured with limbal niche cells (LNCs) in three-dimensional Matrigel (3D Matrigel) in vitro. Methods: MCECs were isolated from central corneas, and limbal epithelial progenitor cells (LEPCs) were isolated from limbal segments with Dispase II. LNCs were isolated and cultured from limbal niche using the collagenase A digestion method and identified with PCK/VIM/CD90/CD105/SCF/PDGFRß. MCECs were cultured on 3D Matrigel (50%, v/v) with or without LNCs for 10 days. Expression of CK12 and p63α and clone formation test were used to compare the progenitor phenotypic changes for MCECs before and after induction using LEPCs as control. Results: Homogeneous LNCs were isolated and identified as spindle shape and adherent to a plastic surface coated with 5% Matrigel. Double immunostaining of the fourth-passage LNCs was uniformly PCK-/VIM+/CD90+/CD105+/SCF+/PDGFRß+. Reverse transcription and quantitative real-time polymerase chain reaction (RT-qPCR) revealed the decrease of PCK expression from the second passage and elevation of Vim, CD90, CD105, SCF, and PDGFRß transcripts from the third passage, and the transcription level of Vim, CD90, CD105, SCF, and PDGFRß was elevated statistically in the fourth passage compared to the first passage (P < 0.01). Both immunofluorescence (IF) staining for cross section and cytospin cells demonstrated that MCECs expressed higher CK12 while lower p63α than LEPCs (P < 0.01). Sphere growth formation was noticed as early as 24 hours in the MCEC + LNC group, 48 hours in the LEPC group, and 72 hours in the MCEC group. The diameters of the spheres were the biggest in the MCEC + LNC group (182.24 ± 57.91 µm), smaller in the LEPC group (125.71 ± 41.20 µm), and smallest in the MCEC group (109.39 ± 34.85 µm) by the end of the 10-day culture (P < 0.01). Double immunostaining with CK12/p63α showed that cells in the sphere formed from MCECs expressed CK12 but not p63α; in contrast, some cells in the MCEC + LNC group expressed CK12, but most of them expressed p63α. RT-qPCR revealed a significant reduction of CK12 transcript but elevation of p63α, Oct4, Nanog, Sox2, and SSEA4 (P < 0.05). Holoclone composed of cubic epithelial cells could be generated in the MCEC + LNC group but not in the other two groups. Conclusions: The data shows that human MCEC cell phenotype could be induced to the dedifferentiation stage when cocultured with LNCs in 3D Matrigel that simulated the microenvironment of limbal stem cells in vitro.

Progress of Individualized Chemotherapy for Gastric Carcinoma Under the Guidance of Genetic Testing.

BACKGROUND: Gastric cancer is a major malignancy that has high incidence rates worldwide. Approximately 30% of patients with gastric cancer have progressed into advanced stages at the time of diagnosis. Chemotherapy is the standard-of-care for most advanced gastric cancer and elicits variable responses among patients. Personalized chemotherapy based on genetic information of individual patients with gastric cancer has gained increasing attention among oncologists for guiding chemotherapeutic regimens. METHODS: This review summarizes recent progress of individualized chemotherapy in gastric cancer guided by pharmacogenomics. Variable medical research search engines, such as PubMed, Google Scholar, SpringerLink and ScienceDirect, were used to retrieve related literature. Only peerreviewed journal articles were selected for further analyses. RESULTS AND CONCLUSION: The efficiency of chemotherapy in patients with gastric cancer is not only determined by chemotherapeutic drugs but is also directly and indirectly influenced by functionally correlative genes. Individual gene alteration or polymorphism remarkably affects patients' responses to particular chemotherapy. Most studies have focused on the influence of single-gene alteration on a selected drug, and only a few works explored the interaction between therapeutics and a panel of genes. Individualized chemotherapy regimens guided by a genetic survey of a multiple-gene panel are expected to remarkably improve the treatment efficacy in patients with advanced gastric cancer and may become the new standard for personalizing chemotherapy for gastric cancer in the near future.

HLA-A*02:07 Allele Associates with Clarithromycin-Induced Cutaneous Adverse Drug Reactions in Chinese Patients.

Genetic risk factors could cause cutaneous adverse drug reactions (cADRs) in patients after treatment with clarithromycin. This study explored the association of HLA class I genes with clarithromycin-cADRs in Han Chinese patients. A total of 12 clarithromycin-cADR patients and 34 clarithromycin-tolerant controls were recruited for the high-resolution genotyping of HLA class I genes (HLA-A, HLA-B and HLA-C). The population controls consisted of 283 Han Chinese retrieved from the MHC database for validated comparison. A molecular docking analysis of HLA-A*02:07 protein and clarithromycin was conducted using glide module with Schrödinger Suite. Among all tested HLA alleles, the carrier frequencies of HLA-A*02:07 (58% versus 5.9%, OR = 22.40, 95% CI = 3.58-139.98, p = 8.20 × 10E-5, pc = 1.1 × 10E-3) and HLA-B*46:01 (50% versus 5.9%, OR = 16.00, 95% CI = 2.59-98.99, p = 0.002, pc = 0.03) were significantly higher in clarithromycin-cADRs than in clarithromycin-tolerant controls. However, when compared to population controls, only HLA-A*02:07, and not HLA-B*46:01, reached statistical significance (58% versus 15.5%, OR = 7.61, 95% CI = 2.31-25.04, p = 1.2 × 10E-4, pc = 1.7 × 10E-3). Furthermore, molecular docking data revealed that clarithromycin could bind to and interact with HLA-A*02:07 in two possible binding situations. These data suggest that HLA-A*02:07 might be a genetic risk factor for developing clarithromycin-cADRs in Han Chinese and serve as a useful biomarker for personalized medicine to prevent clarithromycin-cADRs.