Ferroptosis of chondrocytes is a significant contributor to osteoarthritis (OA), for which there is still a lack of safe and effective therapeutic drugs targeting ferroptosis. Here, we screen for anti-ferroptotic drugs in Food and Drug Administration (FDA)-approved drug library via a high-throughput manner in chondrocytes. We identified a group of FDA-approved anti-ferroptotic drugs, among which vitamin K showed the most powerful protective effect. Further study demonstrated that vitamin K effectively inhibited ferroptosis and alleviated the extracellular matrix (ECM) degradation in chondrocytes. Intra-articular injection of vitamin K inhibited ferroptosis and alleviated OA phenotype in destabilization of the medial meniscus (DMM) mouse model. Mechanistically, transcriptome sequencing and knockdown experiments revealed that the anti-ferroptotic effects of vitamin K depended on growth arrest-specific 6 (Gas6). Furthermore, exogenous expression of Gas6 was found to inhibit ferroptosis through the AXL receptor tyrosine kinase (AXL)/phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) axis. Together, we demonstrate that vitamin K inhibits ferroptosis and alleviates OA progression via enhancing Gas6 expression and its downstream pathway of AXL/PI3K/AKT axis, indicating vitamin K as well as Gas6 to serve as a potential therapeutic target for OA and other ferroptosis-related diseases.

Oral and maxillofacial space infection(OMSI)as a mostly mixed infection,often requires the combination of anti-aerobe and an-ti-anaerobe antibiotics.The use of third-generation quinolones,such as levofloxacin,is limited in OMSI due to the tendon rupture and other serious adverse drug reactions(ADR).In the treatment of a case with OMSI and anaphilactic shock induced by levofloxacin,the association evaluation method of ADR and literature review method participated by clinical pharmacists were used.Suggestions on rational drug use and ADR treatment were gained,the patient was timely rescued from anaphylactic and cured of OMSI.

Liver ischemia-reperfusion injury (IRI) is a significant factor contributing to liver dysfunction following surgical procedures such as liver transplantation and hepatectomy, and its pathogenesis is closely associated with oxidative stress and immune responses. However, effective prevention and therapeutic strategies are still lacking. Short-chain fatty acids (SCFAs), primarily produced by the fermentation of gut microbiota, are the major source of these acids in the human body. Research has indicated that SCFAs play a significant role in oxidative stress and immune response. This review primarily focuses on the advancements on the role of SCFAs, the main metabolic byproducts of gut microbiota, in liver IRI, with a view to provide insights for the development of prevention and treatment strategies for liver IRI.

Liver ischemia reperfusion injury (IRI) is one of the main causes of liver dysfunction or functional failure after liver transplantation or liver resection. As the main organ of lipid metabolism, liver is closely related to lipid metabolic balance. Lipoxygenase is a non-heme iron-containing oxidases that oxidizes polyunsaturated fatty acids to produce hydroxy-eicosanotetraenoic acid. Lipoxygenase is excessively expressed during liver ischemia, causing lipid metabolic disorders. High expression of several proinflammatory cytokines induced by lipoxygenase during liver reperfusion. Lipid peroxidation induced by lipoxygenase leads to the production of lipid oxygen free radicals, which induces iron death mainly characterized by lipid peroxidation, thus affecting apoptosis and tissue damage. This review mainly introduces the latest progress of lipoxygenase in liver IRI.

The review focuses upon the mechanism of exosome derived from mesenchymal stem cells in hepatic ischemia-reperfusion injury(IRI)to provide references for clinical application of exosomes in alleviating hepatic IRI.

Although somatic cells can be reprogrammed to pluripotent stem cells (PSCs) with pure chemicals, authentic pluripotency of chemically induced pluripotent stem cells (CiPSCs) has never been achieved through tetraploid complementation assay. Spontaneous reprogramming of spermatogonial stem cells (SSCs) was another non-transgenic way to obtain PSCs, but this process lacks mechanistic explanation. Here, we reconstructed the trajectory of mouse SSC reprogramming and developed a five-chemical combination, boosting the reprogramming efficiency by nearly 80- to 100-folds. More importantly, chemical induced germline-derived PSCs (5C-gPSCs), but not gPSCs and chemical induced pluripotent stem cells, had authentic pluripotency, as determined by tetraploid complementation. Mechanistically, SSCs traversed through an inverted pathway of in vivo germ cell development, exhibiting the expression signatures and DNA methylation dynamics from spermatogonia to primordial germ cells and further to epiblasts. Besides, SSC-specific imprinting control regions switched from biallelic methylated states to monoallelic methylated states by imprinting demethylation and then re-methylation on one of the two alleles in 5C-gPSCs, which was apparently distinct with the imprinting reprogramming in vivo as DNA methylation simultaneously occurred on both alleles. Our work sheds light on the unique regulatory network underpinning SSC reprogramming, providing insights to understand generic mechanisms for cell-fate decision and epigenetic-related disorders in regenerative medicine.
Male ; Mice ; Animals ; Cellular Reprogramming/genetics* ; Tetraploidy ; Pluripotent Stem Cells/metabolism* ; Induced Pluripotent Stem Cells/metabolism* ; DNA Methylation ; Spermatogonia/metabolism* ; Germ Cells/metabolism*

To construct a prokaryotic promoter report system with wide applicability, a series of pFGH reporter vectors based on lacZ gene and pUC replicon were constructed from plasmid pFLX107 through the replacement of multiple cloning sites and sequence modifications. The plasmid with the lowest background activity was selected as the final report system with the lacZ gene deletion strain MC4100 as the host bacterium, following by testing with inducible promoter araBAD and the constitutive promoter rpsM. The background activity of pFGH06 was significantly lower than that of other plasmids of the same series, and even lower than that of reference plasmid pRCL at 28 °C (P<0.01). Further evaluation tests show that the plasmid pFGH06 could be used to clone and determine the activity of inducible promoter or constitutive promoter, and the complete recognition of the target promoter could be achieved through blue-white selection in the simulation test of promoter screening. Compared with the reported prokaryotic promoter report systems, pFGH06 has the advantages of smaller size, more multiple clone sites, adjustable background activity, high efficiency of promoter screening and recognition, thus with a wide application prospect.
Cloning, Molecular ; Escherichia coli/genetics* ; Genes, Reporter/genetics* ; Genetic Vectors/genetics* ; Lac Operon/genetics* ; Plasmids/genetics* ; beta-Galactosidase/genetics*

Objective To establishing an immortal cell line of familial papillary thyroid carcinoma (FPTC), and explore a new approach for studying familial non-medullary thyroid carcinoma (FNMTC). Methods The specimen from a patient with FPTC was selected, separated, and the primary cells were cultured using DMEM/F12 medium (with TSH, T3, EGF and hydrocortisone). To inducing cell immortalization, the exogenous genes SV40T/TERT were transfected into cells by two ways. RT-PCR was used to detect the expressions of thyroid peroxidase (TPO), thyroid globulin (TG), thyroid stimulating hormone receptor (TSHR) and sodium/iodide co-transporter (NIS). Immunofluorescence method was used to detect the expressions of TPO and GPC3. In order to detect the genomic mutations, the peripheral blood DNA of the patient was extracted. The cell genome was detected. Results The FPTC cells adhered to the plate and showed an irregular polygon shape. The cells can stably grow for six months, FPTC-S (with SV40T transfected) passaged to p26, FPTC cells passaged to p23 and FPTC-ST (with SV40T/TERT transfected) passaged to p19. Both FPTC-S and FPTC-ST can stably express TPO, TG and TSHR in mRNA level. MLH1 R217C mutation existed in the peripheral blood of the patient, and BRAF V600E mutation existed in the primary cultured cells. Either the primary or the immortal cells showed MLH1 R217C mutation. Conclusion This study preliminarily established an immortal cell line of familial papillary thyroid carcinoma with MLH 1 R217C and BRAF V600E mutations. This cell line provides a research model for studying these mutations in FPTC.

Objective To observe the effect of mesenchymal stem cells ( MSC) in treating ischemic diabetic ulcers, and to explore its clinical perspectives. Methods Prepared electro-spinning biomaterials and cultured MSC to study effect of MSC composite biomaterials in vitro by scanning electron microscope,MTT array and influence of MSC conditioned medium on endothelial cells. The use of 5 to 8 week old male C57BL/6J mice were prepared into diabetic mice,femoral artery ligation in the proximal thigh,in dorsal skin full-thickness wounds caused by the diameter 5 mm. Then the effect of MSC composite biomaterials on ischemic diabetic ulcers was determined. Results This study found that the MSC grow well on electro-spinning biomaterials. Cells foot extension and connections between cells were observed by scanning electron microscope. Stimulated by high glucose,growth and proliferation of MSC has a stronger ability on biomaterials. MSC condi-tioned medium on biomaterials increased human umbilical vein endothelial cells proliferation ability. Conclusion MSC composite biomateri-als can effectively improve the treatment effect of MSC on ischemic diabetic ulcers. The study indicated stem cells composite biomaterials have great potential and application prospect in the treatment of ischemic diabetic ulcers healing.

Objective To study the feasibility of model building methods by analyzing the advantages and disadvantages between the two different methods to build off-pump coronary artery bypass graft animal model. Methods Twenty dogs were randomly divided into two groups:brachiocephalic artery group and descending aorta group. Small-caliber heterogeneous vascular vessels were used as bridge vessels. The incision was in the fourth intercostal space of the left chest. Vascular anastomosis was firstly done between the brachiocephalic artery and bridge vessels,or between descending aorta and bridge vessels,prior to coronary vascular and bridge vessels anastomosis. Results The dogs of two groups were not dead during operation. Brachiocephalic artery group and the descending aorta group:aortic vascular anastomosis times were (33.9 ±4.8) min and (29.6 ±3.5) min respectively (P<0.05),coronary vascular anastomosis time were (28.5 ±3.0) min and (28. 1 ± 2. 3) min respectively (P>0. 05). The surgical blood losses of the two groups were (77. 5 ± 16. 2) mL and (66. 5 ± 12. 3) mL re-spectively (P>0. 05). After side clamping descending aorta,femoral blood pressure significantly decreased in descending aorta group,and the two dogs had melena after operation. Conclusion Off-pump coronary artery bypass graft models were both constructed successfully by the two ways. Descending aorta group of femoral artery blood pressure violently fluctuated and had abdominal organs’ ischemia reperfusion in-jury. Though brachiocephalic artery group anastomosis group spent a little longer time,they had stable artery blood pressure during operation. As a result,the way of constructing animal model of brachiocephalic artery group is safer.