Research progress on mitochondria regulating anti-tumor immunity / 浙江大学学报·医学版

Tumor cells adaptively reforge their metabolism to meet the demands of energy and biosynthesis. Mitochondria, pivotal organelles in the metabolic reprogramming of tumor cells, contribute to tumorigenesis and cancer progression significantly through various dysfunctions in both tumor and immune cells. Alterations in mitochondrial dynamics and metabolic signaling pathways exert crucial regulatory influence on the activation, proliferation, and differentiation of immune cells. The tumor microenvironment orchestrates the activation and functionality of tumor-infiltrating immune cells by reprogramming mitochondrial metabolism and inducing shifts in mitochondrial dynamics, thereby facilitating the establishment of a tumor immunosuppressive microenvironment. Stress-induced leakage of mitochondrial DNA contributes multifaceted regulatory effects on anti-tumor immune responses and the immunosuppressive microenvironment by activating multiple natural immune signals, including cGAS-STING, TLR9, and NLRP3. Moreover, mitochondrial DNA-mediated immunogenic cell death emerges as a promising avenue for anti-tumor immunotherapy. Additionally, mtROS, a crucial factor in tumorigenesis, drives the formation of tumor immunosuppressive microenvironment by changing the composition of immune cells within the tumor microenvironment. This review focuses on the intrinsic relationship between mitochondrial biology and anti-tumor immune responses from multiple angles. We expect to explore the core role of mitochondria in the dynamic interplay between the tumor and the host, in order to facilitate the development of targeted mitochondrial strategies for anti-tumor immunotherapy.

Benchmark Dose Assessment for Coke Oven Emissions-Induced Mitochondrial DNA Copy Number Damage Effects / 生物医学与环境科学（英文）

OBJECTIVE@#The study aimed to estimate the benchmark dose (BMD) of coke oven emissions (COEs) exposure based on mitochondrial damage with the mitochondrial DNA copy number (mtDNAcn) as a biomarker.@*METHODS@#A total of 782 subjects were recruited, including 238 controls and 544 exposed workers. The mtDNAcn of peripheral leukocytes was detected through the real-time fluorescence-based quantitative polymerase chain reaction. Three BMD approaches were used to calculate the BMD of COEs exposure based on the mitochondrial damage and its 95% confidence lower limit (BMDL).@*RESULTS@#The mtDNAcn of the exposure group was lower than that of the control group (0.60 ± 0.29 vs. 1.03 ± 0.31; P < 0.001). A dose-response relationship was shown between the mtDNAcn damage and COEs. Using the Benchmark Dose Software, the occupational exposure limits (OELs) for COEs exposure in males was 0.00190 mg/m 3. The OELs for COEs exposure using the BBMD were 0.00170 mg/m 3 for the total population, 0.00158 mg/m 3 for males, and 0.00174 mg/m 3 for females. In possible risk obtained from animal studies (PROAST), the OELs of the total population, males, and females were 0.00184, 0.00178, and 0.00192 mg/m 3, respectively.@*CONCLUSION@#Based on our conservative estimate, the BMDL of mitochondrial damage caused by COEs is 0.002 mg/m 3. This value will provide a benchmark for determining possible OELs.

Mutual promotion of mitochondrial fission and oxidative stress contributes to mitochondrial-DNA-mediated inflammation and epithelial-mesenchymal transition in paraquat-induced pulmonary fibrosis / 世界急诊医学杂志（英文）

@#BACKGROUND: Pulmonary fibrosis (PF) is one of the main causes of death in patients with paraquat (PQ) poisoning. This study aimed to evaluate the relationship between mitochondrial fission and oxidative stress in PQ-induced epithelial-mesenchymal transition (EMT) and PF. METHODS: C57BL/6 mice and MLE-12 cells were exposed to PQ to construct a PF model in vivo and in vitro. Histological changes in the lungs were examined by hematoxylin and eosin (H&E) staining. Mitochondrial morphology was detected by MitoTracker® Deep Red FM or transmission electron microscopy (TEM). Western blotting and immunofluorescence were used to determine the expression of protein. The migration ability of the cells was detected by the cell scratch test. Mitochondrial DNA (mtDNA) levels were assessed by real-time polymerase chain reaction (PCR). Enzyme-linked immunosorbent assay (ELISA) was applied to detect cytokine levels. Superoxide dismutase (SOD) activity and the levels of glutathione (GSH) and malondialdehyde (MDA) were detected by chemichromatometry. RESULTS: PQ exposure caused EMT and PF in vivo and in vitro. PQ destroyed mitochondrial structure and enhanced the expression of dynamin-related protein 1 (Drp1), which were accompanied by oxidative stress. Inhibiting mitochondrial fission using mitochondrial division inhibitor-1 (Mdivi-1), a selective inhibitor of Drp1, attenuated PQ-induced EMT and oxidative damage. Treatment with N-acetyl-L-cysteine (NAC), an antioxidant, reduced Drp1 expression, attenuated mitochondrial structure damage and inhibited PQ-induced EMT and PF. Both Mdivi-1 and NAC treatment markedly suppressed mtDNA release, the expression of Toll-like receptor 9 (TLR9) and phosphorylation (P)-NF-κB p65 as well as cytokines (interleukin 6 [IL-6], interleukin-1β [IL-1β], and tumor necrosis factor-α [TNF-α]) production. CONCLUSION: Mutual promotion of mitochondrial fission and oxidative stress contributes to EMT in PQ-induced PF, which is associated with the mtDNA/TLR9/NF-κB pathway.

Clinical and genetic analysis of essential hypertension with CYB gene m.15024G>A mutation / 浙江大学学报·医学版

OBJECTIVES@#To explore the role of mitochondrial CYB 15024G>A mutation in the development of essential hypertension.@*METHODS@#Mitochondrial genome sequences of hypertensive patients were obtained from previous studies. Clinical and genetic data of a hypertensive patient with mitochondrial CYB 15024G>A mutation and its pedigree were analyzed. Lymphocytes derived from patient and family members were transformed into immortalized lymphoblastoid cell lines, and the levels of adenosine triphosphate (ATP), mitochondrial membrane potential and intracellular reactive oxygen species (ROS) were detected.@*RESULTS@#The penetrance of this essential hypertension family was 42.9%, and the age of onset was 46-68 years old. Mitochondrial genome sequencing results showed that all maternal members carried a highly conserved mitochondrial CYB 15024G>A mutation. This mutation could affect the free energy of mitochondrial CYB for secondary and tertiary structure and protein folding, thereby changing its structural stability and the structure of the electron transfer function area around the mutation site. Compared with the control, the cell line carrying the mitochondrial CYB 15024G>A mutation showed significantly decreased levels of mitochondrial CYB, ATP and mitochondrial membrane potential, and increased levels of ROS (P<0.01).@*CONCLUSIONS@#Mitochondrial CYB 15024G>A mutation may affect the structure of respiratory chain subunits and mitochondrial function, leading to cell dysfunction, which suggests that the mutation may play a synergistic role in essential hypertension.

Research progress of mitochondrial genetics in age-related macular degeneration / 中华实验眼科杂志

Mitochondria are the center of cellular energy metabolism, and their functions are tightly regulated by the nuclear and mitochondria genomes.Potential mechanisms responsible for age-related mitochondrial dysfunction include the accumulation of mitochondrial DNA (mtDNA) damage caused by replication errors or oxidative damage, and the epigenetic changes in mtDNA (mitoepigenetics). These mechanisms are essential for the development and progression of age-related macular degeneration (AMD). Age-related mtDNA damage disrupts energy metabolism and cellular function in the retinal pigment epithelium (RPE) and neuroretinal cells, which further mediates oxidative stress, lysosomal dysfunction and pyroptosis, resulting in RPE degeneration, drusen deposition and retinal inflammation.Mitochondrial genome protection, such as humanin administration, may be a promising preventive or therapeutic target in the early stages of AMD.This review focused on the research progress of the mitochondrial genetic mechanism in AMD pathogenesis and provided new ideas for exploring the prevention and treatment strategies of AMD.

Non-canonical STING-PERK pathway dependent epigenetic regulation of vascular endothelial dysfunction via integrating IRF3 and NF-κB in inflammatory response

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.

Pathologically Elevated-Cyclic Stretch Suppressed Vascular Smooth Muscle Cell Mitochondrial Biogenesis by Down-regulating PGC1α Expression / 医用生物力学

Objective To investigate the effect of pathologically elevated-cyclic stretch induced by hypertension on mitochondrial biogenesis of vascular smooth muscle cells (VSMCs), and the role of PGC1α in this process. Methods The Flexcell-5000T stretch loading system in vitro was applied to VSMCs with a frequency of 1. 25 Hz and an amplitude of 5% or 15% to simulate the mechanical environment under normal physiological or hypertensive pathological conditions respectively. Western blotting and qPCR were used to detect the expression of PGC1α, citrate synthase and mitochondrial DNA (mtDNA) copy number in VSMCs under normal physiological or hypertensive pathological conditions. VSMCs were treated with PGC1α specific activator ZLN005 to promote PGC1α expression or specific interfering fragment siRNA to inhibit PGC1α expression in order to detect the effect on citrate synthase and mtDNA copy number. Results Compared with 5% physiological cyclic stretch, 15% pathologically elevated-cyclic stretch significantly suppressed the expression of PGC1α, citrate synthase and mtDNA copy number in VSMCs. Compared with control group, the protein expression of PGC1α was significantly decreased and increased respectively. When VSMCs transfected with PGC1α siRNA or incubated PGC1α activator ZLN005, the expression of citrate synthase and mtDNA copy number were also significantly down regulated and up-regulated in VSMCs accordingly. Under physiological cyclic stretch conditions, the protein level of PGC1α was significantly down-regulated by PGC1α siRNA, which also significantly down-regulated citrate synthase expression and mtDNA copy number. The protein expression of PGC1α was significantly up-regulated by ZLN005, which also enhanced the expression of citrate synthase and mtDNA copy number. Conclusions The pathological cyclic stretch induced by hypertension significantly down-regulated the expression of citrate synthase and mtDNA copy number via suppressing the expression of PGC1α, resulting in mitochondrial dysfunction of VSMCs. PGC1α may be a potential therapeutic target molecule to alleviate the progression of hypertension.

Population genetics and molecular identification of Crocodylus acutus and C. moreletii (Crocodilia: Crocodylidae) in captive and wildlife populations / Genética de poblaciones e identificación molecular de Crocodylus acutus y C. moreletii (Crocodilia: Crocodylidae) en poblaciones de cautiverio y de vida libre

Abstract Introduction: There is low evidence of genetic diversity and hybridization processes within Crocodylus acutus and C. moreletii populations. Objetive: To evaluate genetic diversity and some phylogenetic relationships in wild and captive populations of C. acutus and C. moreletii using the Barcode of Life Data System (COX1, cytochrome C oxidase subunit 1 gene). Methods: 28 individuals phenotypically like C. acutus located in the state of Guerrero, Oaxaca and Quintana Roo were sampled, as well as animals belonging to C. moreletii located in the states of Tabasco, Campeche, and Quintana Roo. 641 base pairs of nucleotide sequence from COX1 were used to obtain the haplotype and nucleotide diversity per population, and a phylogenetic and network analysis was performed. Results: Evidence of hybridization was found by observing C. moreletti haplotypes in animals phenotypically determined as C. acutus, as well as C. acutus haplotypes in animals classified as C. moreletti. Low haplotypic diversity was observed for C. acutus (0.455 ± 0.123) and for C. moreletii (0.505 ± 0.158). A phylogenetic tree was obtained in which the sequences of C. acutus and C. moreletii were grouped into two well-defined clades. Organisms identified phenotypically as C. acutus but with C. moreletii genes were separated into a different clade within the clade of C. moreletii. Conclusions: There are reproductive individuals with haplotypes different from those of the species. This study provides a small but significant advance in the genetic knowledge of both crocodile species and the use of mitochondrial markers, which in this case, the COX1 gene allowed the detection of hybrid organisms in wild and captive populations. Conservation efforts for both species of crocodiles should prevent the crossing of both threatened species and should require the genetic identification of pure populations, to design effective conservation strategies considering the possibility of natural hybridization in areas of sympatry.

Resumen Introducción: Existe poca evidencia de la diversidad genética y los procesos de hibridación dentro de las poblaciones de Crocodylus acutus y C. moreletii. Objetivo: Evaluar la diversidad genética y algunas relaciones filogenéticas en poblaciones silvestres y cautivas de C. acutus y C. moreletii utilizando el Sistema de Código de Barras de la vida (COX1, subunidad I del gen del citocromo C oxidasa). Métodos: Se muestrearon 28 individuos fenotípicamente similares a C. acutus ubicados en los estados de Guerrero, Oaxaca y Quintana Roo, así como animales pertenecientes a C. moreletii ubicados en los estados de Tabasco, Campeche y Quintana Roo. Se utilizaron 641 pares de bases de la secuencia de nucleótidos de la subunidad I del gen del citocromo C oxidasa para obtener el haplotipo y la diversidad de nucleótidos por población, y se realizó un análisis filogenético y de redes. Resultados: Se encontró evidencia de hibridación al observar haplotipos de C. moreletti en animales determinados fenotípicamente como C. acutus, así como haplotipos de C. acutus en animales clasificados como C. moreletti. Se observó una baja diversidad haplotípica para C. acutus (0.455 ± 0.123) y para C. moreletii (0.505 ± 0.158). Se obtuvo un árbol filogenético en el que las secuencias propias de C. acutus y C. moreletii se agruparon en dos grandes y bien definidos clados. Los organismos identificados fenotípicamente como C. acutus pero con genes de C. moreletii se separaron en un clado diferente dentro del clado de C. moreletii. Conclusiones: Existen individuos reproductores con haplotipos diferentes a los de la especie. Este estudio aporta un pequeño pero significativo avance en el conocimiento genético tanto de las especies de cocodrilos como del uso de marcadores mitocondriales, que, en este caso, el gen COX1 permitió la detección de organismos híbridos en poblaciones silvestres y cautivas. Los esfuerzos de conservación para ambas especies de cocodrilos deben evitar el cruce de ambas especies amenazadas y deben requerir la identificación genética de poblaciones puras, para diseñar estrategias de conservación efectivas considerando la posibilidad de hibridación natural en áreas de simpatría.

Intravitreal injection of mitochondrial DNA induces cell damage and retinal dysfunction in rats

BACKGROUND: Retinal neurodegeneration is induced by a variety of environmental insults and stresses, but the exact mechanisms are unclear. In the present study, we explored the involvement of cytosolic mitochondrial DNA (mtDNA), resulting in the cGAS-STING dependent inflammatory response and apoptosis in retinal damage in vivo. METHODS: Retinal injury was induced with white light or intravitreal injection of lipopolysaccharide (LPS). After light-or LPS-induced injury, the amount of cytosolic mtDNA in the retina was detected by PCR. The mtDNA was isolated and used to transfect retinas in vivo. WB and real-time PCR were used to evaluate the activation of cGAS-STING path-way and the levels of apoptosis-associated protein at different times after mtDNA injection. Retinal cell apoptosis rate was detected by TUNEL staining. Full-field electroretinography (ERG) was used to assess the retinal function. RESULTS: Light injury and the intravitreal injection of LPS both caused the leakage of mtDNA into the cytoplasm in retinal tissue. After the transfection of mtDNA in vivo, the levels of cGAS, STING, and IFN-ß mRNAs and the protein levels of STING, phosph-TBK1, phospho-IRF3, and IFN-ß were upregulated. mtDNA injection also induced the activation of caspase 3 and caspase 9. BAX and BAK were increased at both the mRNA and protein levels. The release of cytochrome c from the mitochondria to the cytosol was increased after mtDNA injection. The wave amplitudes on ERG decreased and retinal cell apoptosis was detected after mtDNA injection. CONCLUSIONS: Cytosolic mtDNA triggers an inflammatory response. It also promotes apoptosis and the dysfunction of the retina.

Gene Flow Patterns of the Aedes aegypti (Diptera: Culicidae) Mosquito in Colombia: a Continental Comparison Suggests Multiple Invasion Routes and Gene Exchange

ABSTRACT In Colombia Aedes aegypti is present in 80% of the country up to 2,300 m; however, little is known of its genetic relations within a country context and, hence, within a broader context, for example, America. The aforementioned, herein, analyzed the gene flow within a context of the Americas, its directionality and genetic diversity of the mitochondrial lineages in the A. aegypti populations for Colombia. This called for the use of the sequences for A. aegypti available of the mitochondrial ND4 gene in the GenBank for Colombia and the American continent. No presence was found of nuclear mitochondrial pseudogenes (NUMTs) for Colombia. It is estimated that in Colombia the gene flow of the A. aegypti populations is occurring from the southeast and northeast toward the center of the country. In comparison with the mitochondrial sequences for America, the vector's haplotypes in Colombia suggest connections between the populations of mosquitoes from the south with those from the north of the continent. The gene flow model at continental scale suggests bidirectional connections between the populations from the north of the continent with those from the south, while at South American scale it proposes the gene flow in all the directions with respect to the Colombian. The Colombian A. aegypti vector monitoring and control strategies must pay special attention to the vector's points of entry into Colombia related with Peru, Venezuela, Brazil, Mexico, and North America to avoid the entry of populations with characteristics like resistance to insecticides or vector competition.

Correlation between mitochondrial DNA copy number and coal-burning-borne endemic fluorosis / 中华地方病学杂志

Objective:To investigate the association between relative mitochondrial DNA copy number (mtDNA-CN) and coal-burning-borne endemic fluorosis (abbreviated as coal-burning-borne fluorosis).Methods:From June 2018 to March 2019, using cross-sectional study, 482 patients with coal-burning-borne fluorosis were selected as the case group in Bijie City, a typical coal-burning-borne fluorosis area of Guizhou Province; meanwhile, 212 healthy individuals from Changshun County, a non-coal-burning-borne fluorosis area in Guizhou Province, were selected as the control group. Questionnaire survey and physical examination were used to collect general condition such as basic information and living habits of the two groups, peripheral venous blood samples were collected, and real-time fluorescence quantitative PCR was used to detect the relative mtDNA-CN in peripheral blood. The correlation between relative mtDNA-CN and coal-burning-borne fluorosis was analyzed by binary and unordered multi-class logistic regression.Results:There were significant differences in the body mass index (BMI), and the distribution of gender rario, marital status and education level between the control group and the case group ( t = 7.91, χ 2 = 5.11, 13.33, 34.32, P < 0.05). The relative mtDNA-CN in the control group was higher than that in the case group [median (quartile): 202 (138, 292) vs 131 (96, 217), Z = - 7.80, P < 0.001]. The results of binary logistic regression analysis [odds ratio (95% confidence interval)] showed that educational level [primary school: 0.572 (0.377 - 0.868), junior high school and above: 0.292 (0.174 - 0.493)], relative mtDNA-CN [131 - < 217: 0.265 (0.144 - 0.488), ≥217: 0.183 (0.100 - 0.335)] and BMI [1.222 (1.142 - 1.307)] were the influencing factors for the risk of coal-burning-borne fluorosis( P < 0.05). In subgroups with different BMI and educational levels, the relative mtDNA-CN was significantly negatively correlated with the risk of coal-burning-borne fluorosis( Ptrend < 0.05), and there was no interaction between mtDNA-CN and BMI and educational levels ( Pinteraction > 0.05). The results of unordered multi-class logistic regression analysis showed that the relative mtDNA-CN were significantly negatively correlated with the risk of dental fluorosis and skeletal fluorosis ( Ptrend < 0.05). Conclusion:The higher the relative mtDNA-CN, the lower the risk of coal-burning-borne fluorosis, suggesting that mtDNA-CN may be a potential biomarker of coal-burning fluorosis.

Research progress on the relationship between mitochondrial function and oral squamous cell carcinoma / 口腔疾病防治

@#Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck. In recent years, the incidence rate has been increasing. Mitochondria are dynamic organelles involved in various cell behaviors in eukaryotic cells. Mitochondrial dysfunction is closely related to tumor development. As a switch that determines cancer cell death, targeting mitochondria has become the focus of OSCC treatment. This article reviews the relationship between mitochondria and tumorigenesis and development, OSCC treatment, and cisplatin resistant OSCC. Current studies have found that mitochondrial dysfunction promotes cell carcinogenesis, and the mitochondrial morphology and function of cancer cells are significantly changed. The increase of mitochondrial fission improves the invasiveness of cancer cells, and mitophagy dysfunction can induce cancer cell apoptosis. The emergence of drugs and the development of nanotechnology in targeted drug delivery systems have opened up new methods for targeting mitochondria to treat OSCC, reducing the side effects of systemic medication. The cisplatin resistance of OSCC is generated through the mitochondrial pathway, and the mitochondrial function and mutation mechanism of mitochondrial DNA are clarified in order to provide new ideas for targeting mitochondria to treat cisplatin resistant OSCC.

A Systematic Review of the Role of Mitochondria in Cleft Pathology: A Forgotten General?

ABSTRACT@#Orofacial clefts (OFC) are one of the most common birth defects that affects the lip, palate, or lip and palate of an infant. The deterioration of clefts is multifactorial involving multiple genes, various interactions from environmental factor and most forgotten, mitochondrial abnormality. The aim of this review is to highlight the importance of mitochondrial activity related to non-syndromic OFC deformity. Despite its important role in cells, the study on mitochondrial activity in cleft pathology was scarce and almost forgotten compared to other genetic investigations. This systematic review was completed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. The literature search was done via the following databases: Google Scholar, Pubmed and Scopus with a total of nine studies of mitochondrial abnormalities were included. We hypothesise that mitochondria play an important role in early craniofacial development. A decreased in its function or activity may result in cleft lip formation. Hence, we would like to shed light on the remarkable role of mitochondria activity in the pathogenesis of non-syndromic OFC.

Population genetic structure of two herds of Aberdeen Angus cattle breed in Colombia / Estructura genética poblacional de dos hatos de ganado bovino Aberdeen Angus en Colombia / Estrutura genética da população de dois rebanhos da raça Aberdeen Angus na Colômbia

Abstract Background: Two biotypes of Aberdeen Angus cattle breed, known as Old Type and New Type, that differ in their origin and beef production are formally recognized. In Colombia, this breed has been commercialized for approximately 80 years. Studies on the origin, kinship and levels of genetic diversity of this breed in Colombian herds are scarce, yet important for planning crossing and management strategies. Objective: To measure the genetic diversity and structure of two Colombian herds of Old Type and New Type biotypes of Aberdeen Angus from Huila and Cundinamarca provinces and assess mitochondrial introgression with other breeds. Methods: A set of ten microsatellites and sequences of the Mitochondrial Control Region were characterized. Estimators of genetic diversity and population differentiation along with tests of population assignment were applied. Results: Nuclear loci were highly polymorphic as shown by the Polymorphic Information Content (0.599) and the Probability of Identity (1.896 10-08). Both populations were highly diverse and clearly differentiated into two groups corresponding to the Old Type and New Type phenotypes. In contrast, mitochondrial data failed to distinguish these two groups and showed extensive admixture. Conclusions: This study optimized a set of ten highly polymorphic nuclear markers that may be used for parentage and population genetic studies of Aberdeen Angus. Genetic differentiation in these loci agreed with phenotypic differences of the Old and New Types. However, mitochondrial data indicated ancestry of multiple European breeds in the origin of Colombian Aberdeen Angus.

Resumen Antecedentes: Dentro de la raza Aberdeen Angus existen dos biotipos conocidos como Old Type y New Type, las cuales difieren en su origen y producción de carne. En Colombia, esta raza se ha venido comercializando desde hace aproximadamente 80 años. No obstante, aún no se han realizado estudios sobre su origen, parentesco y niveles de diversidad genética de esta raza en hatos colombianos, lo cual es importante para planear estrategias de cruce y manejo. Objetivo: Medir la diversidad y estructura genética de dos hatos colombianos de Aberdeen Angus Old Type y New Type de Huila y Cundinamarca y evaluar la introgresión mitocondrial con otras razas. Métodos: Se caracterizó un grupo de diez loci microsatélite y se secuenció la Región Control Mitocondrial. Se aplicaron estimadores de diversidad genética y diferenciación poblacional, junto con pruebas de asignación poblacional. Resultados: Los loci microsatélite fueron altamente polimórficos, tal como lo indicaron el Contenido de Información Polimórfica (0,599) y la Probabilidad de Identidad (1,896 10-08). Las poblaciones evaluadas de Aberdeen Angus en Colombia fueron altamente diversas y se diferenciaron claramente en dos grupos correspondientes a los fenotipos Old Type y New Type. En contraste, los datos mitocondriales no recobraron estos dos grupos y mostraron una amplia mezcla genética. Conclusiones: Este estudio optimizó un grupo de diez marcadores altamente polimórficos que pueden ser usados para estudios de parentesco y genética poblacional de Aberdeen Angus. La diferenciación genética en loci nucleares concordó con las diferencias fenotípicas entre Old y New Types, pero los datos mitocondriales indicaron ancestría de múltiples razas europeas en el origen del Aberdeen Angus colombiano.

Resumo Antecedentes: Dentro da raça Aberdeen Angus há dois biótipos conhecidos como Old Type e New Type, que diferem em sua origem e produção de carne. Na Colômbia, esta raça é comercializada há aproximadamente 80 anos. Entretanto, estudos sobre a origem, o parentesco e os níveis de diversidade genética desta raça em rebanhos colombianos ainda não foram realizados, o que é importante para o planejamento de cruzamentos e estratégias de manejo. Objetivo: Medir a diversidade genética e a estrutura de dois rebanhos colombianos de biótipos de Old Type e New Type de Aberdeen Angus de Huila e Cundinamarca e avaliar a introgressão mitocondrial com outras raças. Métodos: Um grupo de dez loci de microssatélites foi caracterizado e a Região de Controle Mitocondrial foi sequenciada. As estimativas de diversidade genética e diferenciação populacional foram aplicadas, juntamente com testes de designação populacional. Resultados: Os locus microssatélites foram altamente polimórficos, conforme indicado pelo Conteúdo de Infomação Polimórfica (0,599) e Probabilidade de Identidade (1,896 10-08). As populações avaliadas de Aberden Angus na Colômbia eram altamente diversificadas e claramente diferenciadas em dois grupos correspondentes aos fenótipos do Old Type e New Type. Em contraste, os dados mitocondriais não recuperaram esses dois grupos e mostraram um amplo mix genético. Conclusões: Este estudo otimizou um grupo de dez marcadores altamente polimórficos que podem ser usados para estudos genéticos de parentesco e população de Aberdeen Angus. A diferenciação genética nos loci nucleares concordou com as diferenças fenotípicas entre os Old e New Types, mas os dados mitocondriais indicam ancestralidade de várias raças européias na origem do Aberdeen Angus colombiano.

Genetic structure and diversity in Neochen jubata (Aves: Anatidae) from the Araguaia River, GO, Brazil / Estrutura populacional e diversidade genética de Neochen jubata (Aves: Anatidae) no rio Araguaia, GO, Brasil

Abstract: The Orinoco Goose (Neochen jubata) is a few-known and endemic Anatidae to South America, inhabiting sandy beaches along medium and large rivers, with a well-developed riparian forest and in swamp savannas and large freshwater baths. Recent data indicate the presence of longitudinal migratory behavior, and despite them, there are no records on the genetic profile of this species. The Araguaia River region, in the municipality of Luiz Alves, Goiás, receives an undetermined number of ducks seasonally, and there is little information about the individuals who visit this place, constituting the ideal scenario for a study able to offer a genetic overview perspective of this species and to understand the relationship between these individuals better. For this, we genetically characterized 61 individuals sampled in three distinct years of collection using microsatellite molecular markers and mitochondrial DNA. Genetic diversity analyses revealed low levels of heterozygosity for all sampled groups. However, they are within the equilibrium proposed by Hardy-Weinberg (HWE), as inbreeding or drift are not acting in these groups. The parentage analysis supports it, showing a high number of unrelated individuals over the years. AMOVA showed a significant difference among groups. These results may reflect the structure of this migratory species in that region, with the paired differentiation test of individuals from 2013 and 2014 being more similar to each other than those from other years, indicating a possible genetic structure diagnosed by the years of capture. However, there is a high allelic sharing among the three sampled groups, suggesting that these individuals are a population that connects over time and that they have a philopatric relationship with the location. The results found in this study constitute an initial milestone for the genetic knowledge of the mallard duck that should be raised in many other genetic studies.

Resumo: O ganso-do-orinoco (Neochen jubata) é um anatídeo endêmico da América do Sul, cujo habitat são praias arenosas ao longo de rios médios e grandes, com uma vegetação ripária bem desenvolvida e em savanas do pântano com extensos banhados de água doce. Dados recentes indicam a presença de comportamento migratório longitudinal e, apesar destes, não existem registros sobre o perfil genético dessa espécie. A região do rio Araguaia, no município de Luiz Alves, Goiás, recebe um número indeterminado de patos sazonalmente e há poucas informações sobre os indivíduos que visitam este local, constituindo o cenário ideal para um estudo capaz de oferecer uma perspectiva genética geral dessa espécie e também de entender melhor a relação de parentesco entre esses indivíduos. Para tal, caracterizamos geneticamente 60 indivíduos amostrados em três anos distintos de coleta, utilizando marcadores moleculares microssatélites e DNA mitocondrial. As análises de diversidade genética revelaram baixos níveis de heterozigosidade para todos os grupos amostrados. No entanto, eles estão dentro do Equilíbrio proposto por Hardy-Weinberg (HWE), pois a consanguinidade ou a deriva não estão atuando nesses grupos, a análise de parentesco apoia este resultado indicando um alto número de indivíduos não relacionados ao longo dos anos. A AMOVA apresentou diferença significativa entre os grupos. Esses resultados podem refletir a estrutura dessa espécie migratória naquela região, com o teste de diferenciação pareada de indivíduos de 2013 e 2014 sendo mais semelhantes entre si do que os de outros anos, indicando uma possível estruturação genética diagnosticada pelos anos de captura. No entanto, há um alto compartilhamento alélico entre os três grupos amostrados sugerindo que esses indivíduos são uma população que se conecta ao longo do tempo e que têm uma relação filopátrica com o local. Os resultados aqui encontrados constituem um marco inicial para o conhecimento genético do ganso-do-orinoco que contribuirá para novos estudos sobre esta espécie considerada "quase ameaçada" pela IUCN.

Mitochondrial DNA Polymorphism in Zhejiang She Population Based on Next Generation Sequencing / 法医学杂志

Objective To study the genetic polymorphism of whole mitochondrial DNA （mtDNA） genomes in She population in Zhejiang and to explore the maternal genetic structure of the She population. Methods Whole mtDNA genomes of 231 unrelated individuals from She population in Zhejiang Province were sequenced. The number of mutations and population genetics parameters such as, the haplotype diversity （HD）, discrimination power （DP）, and random match probabilities （RMP） were analyzed. The mtDNA haplogroups of Zhejiang She population were classified, and the maternal genetic relationships between She and nine other Chinese populations were estimated. Results In 231 Zhejiang She samples, 8 507 mutations （702 types） were observed and the samples were classified into 94 haplogroups. The HD, DP and RMP values were 0.998 6, 0.994 2 and 0.005 8, respectively. The lowest genetic differentiation degree （Fst=0.006 89） was detected between Zhejiang She population and southern Han population. Principal component analysis （PCA） and median-joining network analysis showed that the genetic distance of Zhejiang She population with Guangxi Yao, Yunnan Dai and Southern Han populations was relatively close, but the population still had some unique genetic characteristics. Conclusion The whole mtDNA genomes are highly polymorphic in Zhejiang She population. The Zhejiang She population contains complex and diverse genetic components and has a relatively close maternal genetic relationship with Guangxi Yao, Yunnan Dai and Southern Han populations. Meanwhile, Zhejiang She population has kept its unique maternal genetic components.

Role of NLRP3 inflammasome and related inflammatory signaling pathways in renal ischemia-reperfusion injury / 器官移植

Renal ischemia-reperfusion injury (IRI) commonly occurs in renal transplantation, which is an important pathophysiological process that causes acute renal failure and severely affects clinical prognosis of the recipients. Inflammatory response plays a critical role in the pathogenesis and pathological process of IRI. Activated NOD-like receptor protein 3(NLRP3) inflammasome can mediate the maturation and release of various pro-inflammatory cytokines, thereby regulating the inflammatory response and relevant cell functions. In this article, the mechanism underlying NLRP3 inflammasome and its related inflammatory signaling pathway in renal IRI were reviewed, aiming to provide novel ideas for clinical prevention and treatment of renal IRI.

Recent progress on the roles of DAMP and NET in organ ischemia-reperfusion injury / 器官移植

Ischemia-reperfusion injury (IRI) is a common pathophysiological phenomenon, secondary to multiple pathological processes, such as organ transplantation, acute kidney injury and myocardial infarction. IRI may significantly aggravate the severity of diseases and increase the fatality of patients. Aseptic inflammation is one of the critical mechanisms of IRI. Damage-associated molecular pattern (DAMP) is a pivotal substance, which mediates aseptic inflammation. After released into extracellular space, it could effectively activate the immune system, and initiate and maintain the inflammatory responses by binding with pattern recognition receptor (PRR). Neutrophil extracellular trap (NET) is a DNA-based network structure released by neutrophils during the process of inflammatory responses, which contains histones and multiple granular proteins. Recent studies have demonstrated that DAMP and NET may aggravate IRI via aseptic inflammation. In this article, relevant studies of DAMP, NET and their relationship in IRI were reviewed, which was of great significance for understanding the pathophysiological mechanism of IRI and studying the corresponding prevention and treatment strategies.

Mitochondrial DNA Targeting Therapies / 中国生物化学与分子生物学报

The mitochondrion is a particularly important organelle in eukaryotic cells. It contains its own genetic material and is coined as “the powerhouse of cells”. Mitochondria are involved in many cellular progresses such as cell signaling and metabolic homeostasis. Its dysfunction is linked to various human diseases, including cancer, neurodegenerative diseases, and diabetes. Mitochondrion has a unique DNA, a small size with 16 569 bp circular genome, encoding only 37 genes, which are key components of the electron transport chain (ETC) and translational machinery. Furthermore, the mutations of mitochondrion DNA correlate with some inherited disease such as Leber’ s hereditary optic neuropathy (LHON) and mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS). There are very few treatments to fully cure these diseases. As a result, researchers are interested in developing a wide range of methods to understand mitochondrial functions. In this review, we mainly focus on works in targeting mitochondrial DNA, including drug modification, material delivery and gene editing.

Mitochondrial DNA-mediated pyroptosis and sepsis / 中国小儿急救医学

Sepsis is a serious life-threatening organ dysfunction disease caused by the host′s unbalanced response to infection, and it′s a common cause of death in intensive care units.Pyroptosis is a kind of necrosis and inflammatory programmed cell death mediated by caspase.Its mechanism can be divided into typical inflammasome activation and atypical inflammasome activation.Caspase-1/11 and Gasdermin-D are the key substrates for pyroptosis.Mitochondrial DNA(mtDNA)as a damage-associated molecular pattern mediates pyroptosis and is associated with severity of sepsis.This review summarized the progress on the relationship between mtDNA-mediated pyroptosis and sepsis.