A case of mitochondrial diabetes mellitus complicated with hypopituitarism and literature review / 中华内分泌代谢杂志

The clinical data of a patient with mitochondrial diabetes mellitus complicated with hypopituitarism were analyzed, the patient′s mitochondrial gene was detected by microarray capture high-throughput sequencing, and the related domestic and foreign literature was reviewed and analyzed. The results showed that the patient had m. 3243 A>G variant on MT-TL1 gene and the clinical features were consistent with mitochondrial diabetes mellitus and hypopituitarism.

MELAS syndrome caused by A3252G mutation in MT-TL1 gene: One case report and literature review / 中华内分泌代谢杂志

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes(MELAS) is one of the most common inherited mitochondrial diseases. This paper reports a rare mutation associated with MELAS syndrome, the m. 3252 A>G mutation in the MT-TL1 gene encoding the mitochondrial tRNALeu(UUR). The 6-year-old girl suffered from recurrent convulsion and lactic acidemia. The mtDNA sequencing detected a variant m. 3252A>G(MT-TL1 gene) in the proband and her maternal relatives. The heteroplasmic levels in peripheral blood and urine sediment were 66.53% and 97.42%, respectively, which were obviously higher than those of her maternal relatives. Together with 3 previously reported cases, the variant m. 3252A>G could be classified pathogenic. All the reported pathogenic variants in MT-TL1 gene were reviewed to explore the genotype-phenotype correlations of pathogenic variants in MT-TL1 gene.

Identification of multi-target anti-cancer agents from TCM formula by in silico prediction and in vitro validation / 中国天然药物

Cancer is a complex disease associated with multiple gene mutations and malignant phenotypes, and multi-target drugs provide a promising therapy idea for the treatment of cancer. Natural products with abundant chemical structure types and rich pharmacological characteristics could be ideal sources for screening multi-target antineoplastic drugs. In this paper, 50 tumor-related targets were collected by searching the Therapeutic Target Database and Thomson Reuters Integrity database, and a multi-target anti-cancer prediction system based on mt-QSAR models was constructed by using naïve Bayesian and recursive partitioning algorithm for the first time. Through the multi-target anti-cancer prediction system, some dominant fragments that act on multiple tumor-related targets were analyzed, which could be helpful in designing multi-target anti-cancer drugs. Anti-cancer traditional Chinese medicine (TCM) and its natural products were collected to form a TCM formula-based natural products library, and the potential targets of the natural products in the library were predicted by multi-target anti-cancer prediction system. As a result, alkaloids, flavonoids and terpenoids were predicted to act on multiple tumor-related targets. The predicted targets of some representative compounds were verified according to literature review and most of the selected natural compounds were found to exert certain anti-cancer activity in vitro biological experiments. In conclusion, the multi-target anti-cancer prediction system is very effective and reliable, and it could be further used for elucidating the functional mechanism of anti-cancer TCM formula and screening for multi-target anti-cancer drugs. The anti-cancer natural compounds found in this paper will lay important information for further study.

Optimization of expression yield in a stable cell line expressing a novel mutated chimeric tissue plasminogen activator (mt-PA)

Abstract The development of stable cell lines producing recombinant proteins is very time-consuming and laborious. One of the practical approaches successfully performed is Fluorescence-Activated Cell Sorting (FACS). A mutated chimeric tissue plasminogen activator (mt-PA) was developed by removing the first three domains of t-PA, insertion of GHRP sequence and mutation toward resistance to plasminogen activator inhibitor-1 (PAI-1). In the current study, a new stable CHO-DG44 cell line producing mt-PA was developed by two sequential clonal selections: FACS and clonal-selection by limiting dilution. Furthermore, the expression was more evaluated using two different expression media. Finally, the high-producing clones were selected based on the dot blot and amidolytic activity test. The transfection efficiency of CHO-DG44 cells was 38% as measured by flow cytometry on green fluorescent protein (GFP). After performing FACS on stable cell pools, the expression yield was increased to fifty-fold. In terms of growth profile, CD-DG44 showed higher viability and cell density results than ProCHO5 medium. The expression of mt-PA was significantly higher in CD-DG44 than in ProCHO5, 765 and 280 IU/mL, respectively. Our data indicated that selection of an appropriate expression medium played a critical role in the development of potent producing stable cells by FACS.

Research Progress on Mechanism of Mitochondrial DNA in Occurrence and Development of Digestive System Malignant Tumors / 肿瘤防治研究

Mitochondrial DNA (mt-DNA) is an important carrier of extranuclear genetic information. Recent research results show that mt-DNA is closely related to the occurrence and metastasis of various malignant tumors, and can be used for early diagnosis and targeted therapy of cancer. Therefore, further research on the mechanism of mt-DNA in digestive system malignant tumors has important clinical significance for screening and identifying tumor molecular markers for anti-tumor drug targets, cancer diagnosis and prognosis analysis. This article reviews the research progress on the potential relationship, clinical application and therapeutic targets of mt-DNA and digestive system malignancies.

Functional metabolomics reveal the role of AHR/GPR35 mediated kynurenic acid gradient sensing in chemotherapy-induced intestinal damage

Intestinal toxicity induced by chemotherapeutics has become an important reason for the interruption of therapy and withdrawal of approved agents. In this study, we demonstrated that chemotherapeutics-induced intestinal damage were commonly characterized by the sharp upregulation of tryptophan (Trp)-kynurenine (KYN)-kynurenic acid (KA) axis metabolism. Mechanistically, chemotherapy-induced intestinal damage triggered the formation of an interleukin-6 (IL-6)-indoleamine 2,3-dioxygenase 1 (IDO1)-aryl hydrocarbon receptor (AHR) positive feedback loop, which accelerated kynurenine pathway metabolism in gut. Besides, AHR and G protein-coupled receptor 35 (GPR35) negative feedback regulates intestinal damage and inflammation to maintain intestinal integrity and homeostasis through gradually sensing kynurenic acid level in gut and macrophage, respectively. Moreover, based on virtual screening and biological verification, vardenafil and linagliptin as GPR35 and AHR agonists respectively were discovered from 2388 approved drugs. Importantly, the results that vardenafil and linagliptin significantly alleviated chemotherapy-induced intestinal toxicity

Dicer Deletion in Astrocytes Inhibits Oligodendroglial Differentiation and Myelination / 神经科学通报·英文版

Increasing evidence has shown that astrocytes are implicated in regulating oligodendrocyte myelination, but the underlying mechanisms remain largely unknown. To understand whether microRNAs in astrocytes function in regulating oligodendroglial differentiation and myelination in the developing and adult CNS, we generated inducible astrocyte-specific Dicer conditional knockout mice (hGFAP-CreERT; Dicer fl/fl). By using a reporter mouse line (mT/mG), we confirmed that hGFAP-CreERT drives an efficient and astrocyte-specific recombination in the developing CNS, upon tamoxifen treatment from postnatal day 3 (P3) to P7. The Dicer deletion in astrocytes resulted in inhibited oligodendroglial differentiation and myelination in the developing CNS of Dicer cKO mice at P10 and P14, and did not alter the densities of neurons or axons, indicating that Dicer in astrocytes is required for oligodendrocyte myelination. Consequently, the Dicer deletion in astrocytes at P3 resulted in impaired spatial memory and motor coordination at the age of 9 weeks. To understand whether Dicer in astrocytes is also required for remyelination, we induced Dicer deletion in 3-month-old mice and then injected lysolecithin into the corpus callosum to induce demyelination. The Dicer deletion in astrocytes blocked remyelination in the corpus callosum 14 days after induced demyelination. Together, our results indicate that Dicer in astrocytes is required for oligodendroglia myelination in both the developing and adult CNS.

Dihydrolipoamide Acetyltransferase Promotes Nucleic Acid Synthesis by Controlling Phosphogluconate Dehydrogenase Acetylation / 中国生物化学与分子生物学报

Mitochondrial pyruvate dehydrogenase complex (PDC) is crucial for glucose homeostasis in mammalian cells‚ decarboxylation of glycolytic intermediate pyruvate to acetyl coenzyme A (acetyl-CoA) in mitochondria. Dihydrolipoyl acetyltransferase (DLAT) is a subunit of the pyruvate dehydrogenase complex. Here‚ we reported that DLAT was commonly increased in lung cancer and its expression was associated with worse clinical outcomes. We found that suppression of DLAT in lung cancer cells resulted in reduced nucleic acid biosynthesis and attenuated cancer cell proliferation through controlling acetylation level of 6-phosphogluconate dehydrogenase (6PGD) ‚ the third enzyme in the oxidative pentose phosphate pathway (PPP) ‚ in which ribulose-5-phosphate (Ru-5-P) is produced for nucleic acid biosynthesis. Together‚ our study contributes to recent interest and discussion cross talk in cancer metabolism‚ which contributes to tumor growth. Future mechanistic studies should lead to the elucidation of the mode of action of DLAT in human lung cancer and establish DLAT as a viable drug target.

Evaluation of the Knowledge, Attitudes and Prevention Practices with Regard to Cutaneous Leishmaniasis Caused by Leishmania aethiopica in Mount Elgon Focus, Kenya

Leishmaniasis has spread beyond the traditional areas of the Rift Valley and North Eastern provinces. There is more evidence of emergence and spread of leishmaniasisin Western Kenya. However, there is currently no comprehensive study on knowledge, attitude and prevention practices on leishmaniasis among the risk populations in the endemic Mount Elgon region of westernKenya. This has hindered the protocol for understanding the epidemiology of leishmaniasis.The descriptive survey design study was carried out from April to June, 2019 and it sought for information on KAP related to cutaneous leishmaniasis (C.L) in Mount Elgon region. Using stratified simple random sampling technique, a total of 340 household participants were selected in the study area. Structured questionnaire was used to collect the data. Regarding the responses given to knowledge, attitude and practice, a score of 1 was given for each right response and 0 for unsure responses. Data analysis was conducted using IBM SPSS version 23 statistical software. Descriptive statistics that include frequency and percentage were used to analyze the results. Out of 340 individuals were participated in our study 214 (62.9%) of the participants were males and 126 (37.1%) were females. The result of the present study in terms of knowledge showed that most of the respondents scored less than four items out of six correctly, hence described as having poor knowledge of CL.With regard to attitude respondents believed that CL was a problem in their area and had positive attitude towards the treatment of the disease. TheOriginal Research Article study also found out that majority of the respondents practiced well, as indicated by scoring positively in more than three items. In terms of plants used in the treatment of the disease,Olea europaea, Kigelia Africana, Terminial mollis, Croton macrostachyus, Tylosema fassoglense andBridella micrantha were mentioned. It was concluded that, people were less knowledgeable, had positive attitude towards the treatment especially using plant extracts could act as the basis for future research on alternative drugs against the disease

Therapeutic effect of adjuvant treatment of acupuncture in a period of day from 7:00 am to 9:00 am on non-dipper essential hypertension / 中国针灸

OBJECTIVE@#To compare the infuences on circadian rhythm of blood pressure in the patients with non-dipper essential hypertension between the combined treatment of time acupuncture and western medication and the simple western medication.@*METHODS@#A total of 70 patients with non-dipper essential hypertension were randomized into an acupuncture plus western medication group (35 cases, 2 cases dropped out) and a western medication group (35 cases). In the western medication group, levamlodipine maleate tablets were taken orally, 2.5 mg each time, once daily. In the acupuncture plus western medication group, on the base of the treatment as the western medication group, acupuncture was applied specially in the period of the day from 7:00 am to 9:00 am. The acupoints included Fengchi (GB 20), Zhongwan (CV 12), Tianshu (ST 25), Hegu (LI 4), Quchi (LI 11), Zusanli (ST 36), etc. Acupuncture was given once daily, 5 treatments a week. The duration of treatment in the two groups was 4 weeks. The clinic blood pressure before and after treatment, 24 h ambulatory blood pressure and the levels of serum melatonin (MT) and 5-serotonin (5-HT) were observed in the two groups.@*RESULTS@#The total effective rate of anti-hypertension was 75.8% (25/33) in the acupuncture plus western medication group, better than 54.3% (19/35) in the western medication group (<0.05). The 24 h average systolic blood pressure, the daytime average systolic blood pressure, the daytime average diastolic pressure, and the nighttime average systolic blood pressure were all reduced after treatment in the two groups (<0.05). The reduction effect of the aforementioned 4 indexes in the acupuncture plus western medication group was much more obvious as compared with the western medication group (<0.05). After treatment, the serum level of MT was increased and 5-HT decreased in the patients of two groups (<0.05). The serum level of MT in the acupuncture plus western medication group was higher than that in the western medication group and the level of 5-HT was lower than the western medication group (<0.05).@*CONCLUSION@#Time acupuncture therapy in the period of the day from 7:00 am to 9:00 am, combined with western medication effectively reduce blood pressure and regulate the levels of serum MT and 5-HT so as to maintain the circadian rhythm of blood pressure in patients with non-dipper essential hypertension. The therapeutic effect of this combined treatment is superior to simple western medication.

Análise sociológica sobre a prática do vôlei de rua em Cuiabá/MT / Sociological analysis on the practice of rua volley in Cuiabá / MT / Sociological analysis on the practice of rua volley in Cuiabá / MT

O artigo tratou do vôlei de rua em Cuiabá/MT como fenômeno sociológico. Procurou desvendar os componentes mediadores do vôlei de rua, bem como identificar os interesses de seus praticantes em Cuiabá/MT, além de evidenciar as histórias de vida de agentes sociais que constroem uma trajetória do lazer, ocupando os espaços comunitários, bairros e as ruas do centro urbano de Cuiabá/MT. A pesquisa buscou também traçar o perfil dos praticantes de vôlei de rua, diferenciar o vôlei de rua do vôlei de quadra e analisar as formas de sociabilidades e disputas em torno dos eventos e jogos de vôlei de rua. A questão norteadora da investigação foi a seguinte: Que estratégias delineiam as maneiras de fazer o "vôlei de rua" em Cuiabá/MT? Trata-se de uma pesquisa qualitativa e descritiva que se utilizou de entrevistas como técnica de coleta de dados. O aporte teórico utilizado é da sociologia contemporânea, os conceitos de campo e habitus de Bourdieu, e cultura e mediação cultural em Geertz, Barbero e Lamizet. O vôlei de rua média as relações sociais entre os atletas, sendo lazer, esporte e veículo produtor de sociabilidades. Dentro dos próprios relatos podemos perceber claramente as diferenças discursivas; uns mais conservadores ou resistentes, outros mais receptivos ao desconhecido, ao novo. Mas o fio condutor de todos os conflitos, provocador da ruptura ressignificante, reside naquele ato de expor publicamente o nome de jogadores que antes na quadra não tinham nenhuma relevância e no ambiente da rua (vôlei de rua) serem os reis da rua.

The article deals with street volleyball in Cuiabá / MT as a sociological phenomenon. It seeks to uncover the mediating components of street volleyball, as well as to identify the interests of its practitioners in Cuiabá / MT, as well as to highlight the life histories of social agents who build a leisure path, occupying community spaces, neighborhoods and the streets of urban center of Cuiabá / MT. The research also sought to outline the profile of street volleyball practitioners, to differentiate street volleyball from volleyball court and to analyze the forms of sociability and disputes surrounding street volleyball events and games. The guiding question of the investigation was the following: What strategies outline the ways of doing "street volleyball" in Cuiabá / MT? This is a qualitative and descriptive research that used interviews as a data collection technique. The theoretical contribution used is contemporary sociology, Bourdieu's field concepts and habitus, and cultural culture and mediation in Geertz, Barbero and Lamizet. Street volleyball mediates social relations among athletes, being leisure, sport and sociability vehicle. Within the own reports we can clearly perceive the discursive differences; some more conservative or resistant, others more receptive to the unknown, to the new. But the guiding thread of all conflicts, which provoked the resigning rupture, lies in that act of publicly exposing the name of players who previously had no relevance in the court and in the street environment (street volleyball) are the kings of the street.

Effects of mindfulness-based stress reduction combined with music therapy on pain, anxiety, and sleep quality in patients with osteosarcoma

Objectives: To evaluate the effects of mindfulness-based stress reduction (MBSR) combined with music therapy (MT) on clinical symptoms in patients with osteosarcoma. Methods: Patients diagnosed with osteosarcoma were assessed for eligibility. A total of 101 patients were ultimately randomized into the intervention and control groups. Both groups received routine care. Eight sessions of MBSR and MT psychotherapy were conducted in the intervention group, while the control group received no psychological intervention. Patients were assessed regarding pain, anxiety, and sleep quality at two distinct stages: before and after the intervention. Results: There were no significant differences in sociodemographic and clinical parameters between the intervention and control groups at baseline. The intervention program significantly alleviated psychological and physiological complications in patients with osteosarcoma. Specifically, the study revealed that 8 weeks of the combined MBSR/MT intervention effectively reduced pain and anxiety scores and improved the quality of sleep in patients. Conclusion: MBSR combined with MT significantly alleviated clinical symptoms, and could be considered a new, effective psychotherapeutic intervention for patients with osteosarcoma.

Authentication of commercially available frozen shrimp meats using DNA barcoding

Shrimps and prawns are quite nutritious and provide quality protein, omega-3 fatty acids, certain antioxidants,vitamins, and minerals like iodine. Therefore, they are healthy food for human consumption. In order to findout fish fraud in value-added products, in this study, six frozen shrimp species packed and sold by differentcommercial companies were purchased, correctly identified using DNA barcoding of mt-COI gene, and thesequences were authenticated properly with the GenBank. The genomic DNA isolated from frozen shrimpsamples showed greater than 10 kb. Their amplified products showed 564–770 bp of mt-COI gene. The BLASTresults for the labeled frozen shrimp sample Litopenaeus vannamei showed maximum similarity (99%–100%)with the same species sequences available with NCBI database. Five unlabeled sample sequences (two samplestaken from two independent packets, and three samples taken from one mixed shrimp packet) showed maximumsimilarity with the sequences available in the NCBI database and exactly identified as Fenneropenaeusmerguiensis, Penaeus monodon, Fenneropenaeus indicus, Penaeus semisulcatus, and P. monodon, respectively.These six sequences showed more variable amino acid sites than the identical and similar amino acid residueswithin themselves. The AT biases (61.5%–67.51%, P. semisulcatus and P. monodon taken from unlabeledmixed packet) and GC biases (32.9%–38.6%, P. monodon and P. semisulcatus) varied among these six speciessequences, which indicated less NUMTs gene. The interspecies divergence rate calculated for these six speciesranged between 0.434 and 3.401 (L. vennamei vs. F. indicus, and F. merguiensis vs. P. monodon, taken fromunlabeled independent packet). Thus, it is recommended that DNA barcoding of mt-COI gene can be used toidentify any unlabeled or labeled shrimp/prawn/seafood available in the market to avoid fish fraud

Diagnostic value of combined detection of MT1-MMP, LncRNA SNHG15 and YAP in thyroid carcinoma / 国际检验医学杂志

Objective To explore the diagnostic value of combined detection of MT1-MMP, LncRNA SNHG15and YAP in thyroid carcinoma.Methods A total of 186thyroid carcinoma patients from July 2015to July 2017were selected as the observation group and 50healthy patients were selected as control group.The expression levels of MT1-MMP, LncRNA SNHG15, and YAP in tissues of the two groups were compared.The relationships between the clinical pathological parameters of thyroid carcinoma and the expression levels of MT1-MMP, LncRNA SNHG15, YAP were analyzed.Results The positive rate of MT1-MMP, YAP and LncRNA SNHG15in observation group were significantly higher than those in control group (P<0.05) .The expression level of YAP in tumors larger than 2cm diameter was significantly higher than that in tumors less than 2cm (P<0.05) .The expression level of YAP and LncRNA SNHG15with envelope infiltration were significantly higher than those without envelope infiltration (P<0.05) .The expression level of MT1-MMP in lymph node metastasis group was significantly higher than that in non-lymphatic metastasis group (P<0.05) .The expression level of YAP in gradesⅢandⅣof TNM were significantly higher than those in gradesⅠandⅡ (P<0.05) .Conclusion High expression level of MT1-MMP is associated with infiltration of thyroid carcinoma capsules and lymphatic metastasis.YAP is associated with greater proliferative capacity of papillary thyroid carcinoma, and LncRNA SNHG15is closely associated with infiltration of capsules.

Effects of melatonin on excitability of pyramidal neurons in prefrontal cortex and the role of MT1R-cAMP-PKA signaling pathway / 中华麻醉学杂志

Objective To evaluate the effects of melatonin on the excitability of pyramidal neurons in the prefrontal cortex and the role of melatonin receptor 1 (MT1 R)-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway.Methods Brains were obtained from male SpragueDawley rats between 14 and 21 days after birth.The brain slices of 350-μm thick were prepared and placed in artificial cerebrospinal fluid.The brain slices were divided into 5 groups (n =6 each) using a random number table method:control group (C group),melatonin group (M group),MT1/2R antagonist luzindole plus melatonin group (L+M group),MT2R antagonist 4P-PDOT plus melatonin group (P+M group) and PKA inhibitor Rp-cAMPS plus melatonin group (R+M group).Cells were perfused for 2 min with artificial cerebrospinal fluid in group C.Cells were perfused for 2 min with 1 μmol/L melatonin in group M.Cells were perfused for 2 min with the mixture of 1 μmol/L MT1/2R antagonist luzindole and 1 μmol/L melatonin in group L+M.Cells were perfused for 2 min with the mixture of 1 μmol/L MT2R antagonist 4P-PDOT and 1 μmol/L melatonin in group P+M.In group R+M,1 mmol/L PKA inhibitor Rp-cAMPS was continuously added to the pipette solution,and cells were perfused for 2 min with 1 μmol/L melatonin.The whole-cell patch-clamp technique was used to record the membrane potential and clamp current of pyramidal neurons in the prefrontal cortex.Results Compared with group C,the clamp current was significantly increased,and the membrane potential was decreased in group M (P＜0.05).Compared with group M,the clamp current was significantly decreased,and the membrane potential was increased in L + M and R + M groups (P＜0.05),and no significant change was found in the clamp current or membrane potential in group P+M (P＞0.05).Conclusion Melatonin inhibits the excitability of pyramidal neutrons in the prefrontal cortex,and the mechanism is related to activating MT1 R-cAMP-PKA signaling pathway.

Inhibitory effect of polyethylenimine derivative pen mediated oligodeoxynucleotide mt01 delivery on experimental rat tooth movement / 吉林大学学报(医学版)

 Objective:To investigate the partial delivery ability in vivo of oligonucleotide MT01 mediated by polyethyleneimine(PEI) derivative PEN, and to illuminate its effect on the alveolar bone reconstruction and the biological safety in the rats with experimental tooth movement. Methods:Forty-eight Wistar male rats were randomly divided into PEN,MT01, sulfuration-modified MT01 (MT01s), and PEN/MT01 groups. The rat experimental tooth model was established, and the above four drugs were injected into the mesial buccal mucosa of the first molar in the left sides of the rats as drug intervention sides,and the PBS were injected into the mesial buccal mucosa of the first molar in the right sides as PBS control sides;once every 3 d. After 14 d, the rats were sacrificed. HE staining was used to detect the histopathological changes of important organs of the rats;the photos and X-ray films were applied to measure the distance of tooth movement, and RT-PCR was used to detect the expression levels of the osteogenic marker genes Runt-related transcription factor 2(Runx2),special protein 7(SP7) and osteocalcin(OCN) mRNA. Results:After local injection of the above drugs, no obvious inflammatory cell infiltration and structural differences were found in the main organs of the rats and no obvious abnormalities were found in all organs tissues. Compared with the PBS control sides, the movement distance of the first molars in the drug intervention sides in MT01, MT01s, and PEN/MT01 groups was reduced (P0.05). The data of the distance between the two teeth of the rats in various groups was PEN/MT01 group > MT01s group > MT01 group>PEN group, and the difference between PEN/MT01 group and MT01s group was statistically significant (P0.05). Conclusion:PEI derivative PEN can transfer MT01 into the cell safely and efficiently; it can increase the expression levels of Runx2, SP7 and OCN mRNA in the periodontium tissue and decrease the tooth movement distance in the experimental tooth movement rats.

Leigh Syndrome Due to mtDNA Pathogenic Variants

Abstract Leigh syndrome is a devastating neurodegenerative disease, typically manifesting in infancy or early childhood. Hallmarks of the disease are symmetrical lesions in the basal ganglia or brain stem on MRI, and a clinical course with rapid deterioration of cognitive and motor functions. It is genetically heterogeneous, causative mutations have been disclosed in mitochondrial DNA and nuclear genes involved in the process of energy production in the mitochondria .We investigated the whole mitochondrial DNA in three Brazilian patients with LS, based on their clinical and biochemical data, with the aim to identify the disease-causing mutations. In two of the patients, with complex I deficiency, a novel heteroplasmic variant m.4142G>T (p.R279L) in MT-ND1 and a recurrent homoplasmic mutation m.10197G>A (p.A47T) in MT-ND3 were identified. In the remaining patient, with complex IV deficiency, a de novo heteroplasmic variant in MT-CO1 m.6547T>C (p.L215P) was found. The molecular investigation in mitochondrial diseases have shifted their focus from mitochondrial DNA to nuclear DNA, however, mtDNA protein-coding genes are one of the important genetic causes of mitochondrial disorders for Leigh syndrome. This study expands the molecular and clinical spectrum associated with this disease.

Tuberculosis intestinal de difícil decisión diagnóstica y terapéutica / Intestinal tuberculosis of difficult diagnostic decision and therapeutic

En este reporte se describe un caso de tuberculosis intestinal (TBCI) de difícil decisión diagnóstica y terapéutica, en el cual se indicó un protocolo de tratamiento anti TBC durante 6 meses con resolución clínica, paraclínica y endoscópica(AU)

In this report we describe a case of intestinal Tuberculosis of difficult diagnostic and therapeutic decision which received anti-TBC treatment for 6 months with clinical, paraclinical and endoscopic resolution(AU)

Two new diphenyl ether derivatives from Penicillium chrysogenum MT-12, an endophytic fungus isolated from Huperzia serrata / 中草药

Objective To investigate the chemical constituents from Penicillium chrysogenum MT-12, an endophytic fungus isolated from Huperzia serrata. Methods The compounds were isolated and purified by using various column chromatographies including silica gel, Sephadex LH-20, and semi-preparative HPLC. The structures were established using extensive spectroscopic techniques such as IR, MS, and NMR. The anti-inflammatory and AChE inhibitory activities of all the isolates were also preliminarily investigated by using in vitro models. Results Eight diphenyl ether derivatives including penicichrysogenillide A (1), penicichrysogenillide B (2), talaromyone A (3), isopenicillide (4), penicillide (5), hydroxypenicillide (6), purpactin A (7), and penicichrysogenillide C (8) were isolated from the solid fermentation cultures of P. chrysogenum MT-12. Conclusion Compounds 1 and 2 are new compounds, and this is the first report for the isolation of compound 3 from Penicillium species and compounds 4-8 from P. chrysogenum. Compounds 1 and 2 exhibited inhibitory activities anginst the nitric oxide production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells with IC50 value of (72.6 ± 2.3) μmol/L and (41.2 ± 1.4) μmol/L, respectively. In contrast, all the compounds didn't exhibit inhibitory activities on AChE at the concentration of 100 μmol/L.

Comparison of hepatotoxicity and toxic mechanisms of matrine and oxymatrine using in vivo and in vitro models / 中国比较医学杂志

Objective To compare the hepatotoxicity of matrine (MT) and oxymatrine (OMT) and explore the severity and characteristics of their toxicity, and to preliminarily elucidate their toxic mechanisms. Methods Liver cell line LO-2 cells were treated with acetaminophen (APAP), matrine and oxymatrine for 24 h, and the IC values, the contents of enzymes in the liver cells, the pathological changes, the contents of malondialdehyde (MDA) and glutathione (GSH) and the cell apoptosis rate were detected. In addition, adult zebrafish were treated with APAP, matrine and oxymatrine for 96 h, and the LC50 values, the pathological morphology of the liver cells, the contents of MDA and GSH and the apoptosis rate were detected. Meanwhile, the expression of oxidative stress-related gene, zgc: 136383, and the apoptosis-related genes, EIF4EBP3 and zgc: 123120, was also detected. Results Matrine and oxymatrine had toxic effects on liver cells in vitro. The IC50 value of matrine was 5. 3 mmol/L, and that of oxymatrine was ＞ 19 mmol/L. The contents of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in the liver cells treated with matrine or oxymatrine were increased, and the cells appeared swollen, with an increase in the MDA level and a decrease in the GSH level. The cell apoptosis rate was also increased (P ＜ 0. 05). Furthermore, matrine and oxymatrine had toxic effects on the zebrafish. The LC50 value of matrine was 0. 41 mmol/L, and that of oxymatrine was ＞3. 8 mmol/L. The hepatocytes of zebrafish treated with matrine and oxymatrine appeared vacuolization in a mild to moderate degree, with an increase of the MDA content and a decrease of the GSH content. The cell apoptosis rate was increased (P ＜0. 05 for all). Expression of the oxidative stress-related gene zgc: 136383 (P ＜ 0. 05) and the apoptosis-resistant gene EIF4EBP3 (P ＜ 0. 05) was down-regulated by matrine, but that of the apoptosis-promoting gene zgc: 123120 was up-regulated (P ＜ 0. 05). Conclusions Results of the experiments using liver cells in vitro are consistent with those using the in vivo zebrafish model. Matrine (MT) and oxymatrine (OMT) both have hepatotoxicity, with similar toxic characteristics, and the toxicity of matrine is greater than oxymatrine. The mechanism of their hepatotoxicity is related with oxidative stress and cell apoptosis. Matrine reduces lipid transportation and activates oxidative stress reactions through down-regulation of gene zgc: 136383. In addition, matrine induces apoptosis in the liver cells via up-regulation of the apoptosis-promoting gene zgc: 123120 and down-regulation of the apoptosis-resistant gene EIF4EBP3.