NLRP1 inhibits lung adenocarcinoma growth through mediating mitochondrial dysregulation in an inflammasome-independent manner

NLRP1, the first identified inflammasome-forming sensor, is thought to be involved in cancer, yet its definite function in lung adenocarcinoma (LUAD) remains unclear. Herein, we explored the expression and function of NLRP1 in LUAD. Decreased NLRP1 expression was identified in LUAD, which was associated with a poor prognosis. Overexpression of NLRP1 inhibited tumor growth in vitro and in vivo. Mechanically, this effect was observed regardless of inflammasome activation. Further studies revealed that overexpression of NLRP1 downregulated the phosphorylation of DRP1 and promoted mitochondrial fusion, which was mediated by inhibition of NF-κB activity. NF-κB agonist could neutralize the effect of NLRP1 on mitochondrial dynamics. In addition, LUAD sensitivity to cisplatin was enhanced by decreased mitochondrial fission resulting from up-regulated NLRP1. In conclusion, our findings demonstrated an unexpected role of NLRP1 in LUAD by modulating mitochondrial activities, which provides strong evidence for its potential in LUAD treatment.

Mitochondrial transplantation as a promising therapy for mitochondrial diseases

Mitochondrial diseases are a group of inherited or acquired metabolic disorders caused by mitochondrial dysfunction which may affect almost all the organs in the body and present at any age. However, no satisfactory therapeutic strategies have been available for mitochondrial diseases so far. Mitochondrial transplantation is a burgeoning approach for treatment of mitochondrial diseases by recovery of dysfunctional mitochondria in defective cells using isolated functional mitochondria. Many models of mitochondrial transplantation in cells, animals, and patients have proved effective via various routes of mitochondrial delivery. This review presents different techniques used in mitochondrial isolation and delivery, mechanisms of mitochondrial internalization and consequences of mitochondrial transplantation, along with challenges for clinical application. Despite some unknowns and challenges, mitochondrial transplantation would provide an innovative approach for mitochondrial medicine.

Fauna of scrub typhus vector chigger mites in Yunnan Province / 中国热带医学

@#Abstract: Chigger mites belong to the phylum Arthropoda, class Arachnida, sub-class Acari, order Parasitiformes, family Trombiculidae and Leeuwenhoekiidae, with a wide range of species. There are more than 3 700 known species of mites globally, of which 531 species in 46 genera from three sub-families have been recorded in China, and 320 species of chigger mites recorded from 3 subfamilies and 32 genera in Yunnan Province. At this stage, chigger mites are the only vectors of scrub typhus, with about 60 species worldwide being potential vectors. Six vectorial mite species have been confirmed in China, including Leptotrombidium deliense, L.scutellare, L.rubellum, L.sialkotense, L.kaohuense, L.insulare. Yunnan Province has reported five vectorial mite species, including the previously-mentioned five species except for L.sialkotense. The zoogeographic study divided Yunnan Province into 5 zoogeographic areas, namely, Central Hengduan Mountains subregion, Southern Hengduan Mountains subregion, Eastern Yunnan Plateau subregion, Western Yunnan Plateau subregion, Southern Yunnan Mountainous subregion. The Southern Hengduan Mountains subregion has the highest number of known genera and species of scrub typhus and the highest number of scrub typhus cases, with 216 species in 22 genera from 3 subfamilies, and all 5 species of vector scrub typhus were distributed. Southern Yunnan Mountain subregion has the least number of mite species, with 91 species in 12 genera from three sub-families, with L. scutellare being the dominant vectorial mite species across the province. Due to suitable natural geographic conditions in Yunnan Province, vectorial mites can propagate rapidly, leading to a large number of scrub typhus cases. According to statistics, the number of scrub typhus cases in Yunnan Province has rapidly increased, with 15.40 times, 20.64 times and 28.91 times more cases in 2016, 2017 and 2018 respectively than in 2006. Scrub typhus remains a serious public health problem in Yunnan Province, posing a threat to the health of the local population. Therefore, prevention and control efforts should continue to focus on the affected areas and the general public.

Effects of a 4-week micro-hyperbaric oxygen intervention on oxidation-antioxidation system function / Efectos de la intervención con oxígeno micro-hiperbárico durante 4 semanas en la función del sistema oxidación-antioxidación / Efeitos da intervenção de oxigênio micro-hiperbárico de 4 semanas na função do sistema oxidante-antioxidante

ABSTRACT Introduction Hyperbaric oxygen intervention has an important effect on the function of the body's oxidation-antioxidant system. Objective To verify the effects of a 4-week micro-hyperbaric oxygen intervention on oxidation-antioxidation system function in skeleton athletes. Methods The experimental group underwent a 1.3 ATA HBO intervention for 4 weeks and the control group underwent natural recovery. The levels of MDA, PC, SOD, CAT, GSH-PX, T-AOC, BU, CK, T, and C of the two groups were measured at Week 0, Week 2, and Week 4. Results The MDA, PC, and CK of the Exp group were significantly lower than Con group (P < 0.05) in Week 4. The SOD, CAT, and T-AOC of the Exp group were significantly higher in Week 4 than in Week 0 (P < 0.05) and significantly higher than the Con group values (P < 0.05). Conclusions A four-week 1.3 ATA HBO intervention decreased the level of oxidative stress, increased the activity of antioxidant enzymes, and reduced the degree of exercise fatigue in skeleton athletes. Level of Evidence II; Therapeutic studies - Investigating treatment results.

RESUMEN Introducción La intervención con oxígeno hiperbárico tiene un efecto importante en la función del sistema oxidación-antioxidación del organismo. Objetivo Verificar los efectos de una intervención con oxígeno micro-hiperbárico durante 4 semanas en la función del sistema oxidación-antioxidación en atletas de skeleton. Métodos El grupo de prueba se sometió a una intervención con oxígeno micro-hiperbárico a 1,3 ATA durante 4 semanas, 4 veces a la semana, y el grupo de control se sometió a una recuperación natural. Se midieron los niveles de malondialdehído (MDA), carbonilo proteico (PC), superóxido dismutasa (SOD), catalasa (CAT), glutatión peroxidasa (GSH-PX), capacidad antioxidante total (T-AOC), urea en sangre (BU), creatina quinasa (CK), testosterona (T), y cortisol (C) en la semana 0, en la semana 2 y en la semana 4 para ambos grupos de atletas. Resultados Los valores de MDA, CP y CK del grupo de prueba fueron significativamente inferiores a los del grupo de control (p <0,05) en la semana 4. Los valores de SOD, CAT y T-AOC fueron significativamente mayores en el grupo de prueba en la semana 4 que en la semana 0 (p < 0,05) y significativamente mayores que los valores del grupo de control (p < 0,05) Conclusión: La intervención con oxígeno hiperbárico a 1,3 ATA durante 4 semanas redujo significativamente los niveles de estrés oxidativo, aumentó la actividad de las enzimas antioxidantes y redujo los niveles de fatiga relacionada con el ejercicio en los atletas de skeleton. Nivel de evidencia II; Estudios terapêuticos - Investigación de los resultados del tratamiento.

RESUMO Introdução A intervenção de oxigênio hiperbárico tem um efeito importante na função do sistema oxidativo-antioxidante do corpo. Objetivo Verificar os efeitos de uma intervenção de oxigênio micro-hiperbárico de 4 semanas na função do sistema oxidante-antioxidante em atletas de skeleton. Métodos O grupo de teste foi submetido a uma intervenção de oxigênio micro-hiperbárico a 1,3 ATA de 4 semanas, 4 vezes por semana e o grupo controle passou por recuperação natural. Os níveis de malondialdeído (MDA), proteína carbonila (PC), superóxido dismutase (SOD), catalase (CAT), glutationa peroxidase (GSH-PX), capacidade antioxidante total (T-AOC), uréia sanguínea (BU), creatina quinase (CK), testosterona (T) e cortisol (C) foram medidos na semana 0, semana 2 e semana 4 para ambos os grupos de atletas. Resultados MDA, PC e CK do grupo de teste foram significativamente menores do que os valores do grupo controle (p <0,05) na semana 4. SOD, CAT e T-AOC foram significativamente maiores no grupo de teste na semana 4 do que na semana 0 (p < 0,05) e significativamente maiores do que os valores para o grupo controle (p < 0,05). Conclusão A intervenção de oxigênio micro-hiperbárico de 4 semanas a 1,3 ATA reduziu significativamente os níveis de estresse oxidativo, aumentou a atividade enzimática antioxidante e reduziu os níveis de fadiga relacionada ao exercício nos atletas de skeleton. Nível de evidência II; Estudos terapêuticos - Investigação dos resultados do tratamento.

A Report of Chigger Mites on the Striped Field Mouse, Apodemus agrarius, in Southwest China

Based on the field investigations in 91 investigation sites (counties) in southwest China between 2001 and 2019, the present paper reported the chigger mites on A. agrarius mice in southwest China for the first time by using a series of statistical methods. From 715 striped field mice captured in 28 of 91 investigated sites, only 255 chiggers were collected, and they were identified as 14 species, 6 genera in 3 subfamilies under 2 families. Of 715 A. agrarius mice, only 24 of them were infested with chigger mites with low overall prevalence (PM=3.4%), overall mean abundance (MA=0.36 mites/host) and overall mean intensity (MI=10.63 mites/host). The species diversity and infestation of chiggers on A. agrarius were much lower than those previously reported on some other rodents in southwest China. On a certain species of rodent, A. agrarius mouse in southwest China seems to have a very low susceptibility to chigger infestations than in other geographical regions. Of 14 chigger species, there were 3 dominant species, Leptotrombidium sialkotense, L. rupestre and Schoengastiella novoconfuciana, which were of aggregated distribution among different individuals of A. agrarius hosts. L. sialkotense, one of 6 main vectors of scrub typhus in China, was the first dominant on A. agrarius. The species similarity of chigger mites on male and female hosts was low with CSS=0.25, and this reflects the sex-bias of different genders of A. agrarius mice in harboring different chigger species.

Recent advances in the research of broad-spectrum antiviral agents / 药学学报

Viral infections have always threatened human health. Broad-spectrum antiviral agents (BSAs) can either target host proteins that are essential for viral replication, or act on multiple viruses or multiple genotypes of the same virus. More importantly, BSAs could reduce the possibility of drug resistance. From the perspective of medicinal chemistry, this review summarizes recent advances in the research of broad-spectrum antiviral drugs with privileged structures or targeting specific targets in the viral life cycle.

The effects of optical genetic techniques on new neurons through the Wnt/β-Catenin pathway / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects of optical genetic techniques on new neurons through the Wnt/β-Catenin pathway.@*METHODS@#Neural stem cells (ESCs)were extracted from the cerebral cortex of fetal rat and transfected by lentivirus carrying DCX-ChR2-EGFP gene and the expression of DCX of newborn neurons differentiated from neural stem cells were observed. All cells were divided into 3 groups(n=9): control group, NSCs+EGFP and NSCs+ChR2 groups. The control group was normal cultured NSCs (NSCs group); the neural stem cells in NSCs+EGFP group were transfected with lentivirus carrying EGFP gene. The neural stem cells in NSCs+ChR2 group were infected with lentivirus carrying DCX-ChR2-EGFP gene. After 48 hours of lentivirus infection, 470 nm blue laser irradiation was performed for 3 consecutive days. NeuN positive cell density(the maturation of neural stem cells)and the ratio of NeuN/Hoechst in each group were observed. Western blot was used to detect the expression levels of MAP2, NeuN, Neurog2, NeuroD1 and GluR2. Western blot was used to detect the expressions of β-catenin and TCF4 associated with Wnt/β-catenin signaling channel. Verapamil (100 μmol/L, L-type calcium channel blockers) and Dkk1 (50 μg/ml, β-catenin inhibitor) were used to treat stem cells of the NSCs+ChR2 group and then the expressions of MAP2, NeuN, Neurog2, NeuroD1 and GluR were detected by Western blot.@*RESULTS@#After 3 days of 470 nm blue laser irradiation, NeuN positive cell density(the maturation of neural stem cells)and the ratio of NeuN/Hoechst, the expression levels of the protein MAP2, NeuN, Neurog2, NeuroD1, GluR and the protein β-catenin and TCF4 associated with Wnt/β-catenin signaling channel detected by Western blot were significantly increased in the group of NSCs+ChR2, compared with NSCs and NSCs+EGFP groups. The expressions of MAP2, NeuN, Neurog2, NeuroD1 and GluR were remarkably decreased after treated by verapamil and Dkk1 in the group of NSCs+ChR2. It was proved that the opening of ChR2 channel producing cationic influx promoted the maturation of neural stem cells and induced by the Wnt/β-catenin signaling pathway.@*CONCLUSION@#Optical genetic promoted the maturation of newborn neurons through the Wnt/β-catenin signaling pathway.

Comparative study on sepsis models induced by Escherichia coli subtypes / 天津医药

Objective To investigate the degrees of injury severity of sepsis models made by different kinds of Escherichia coli. Methods The 152 mice were randomly divided into control group, DH5α group, 44102 group, and 25922 group, with 38 rats in each group. DH5α group, 44102 group and 25922 group were intraperitoneally injected with 300 μL of Escherichia coli DH5α, 44102 and 25922 at the concentration of 1.0 × 109CFU/kg to prepare sepsis models of different kinds of Escherichia coli. Control group was injected intraperitoneally with the same amount of normal saline. (1) After 8 h, four mice were taken from each group for peripheral blood bacterial culture . (2) After 12 h, ten mice in each group were used for measuring serum levels of TNF-α and IL-6 by enzyme-linked immunosorbent assay (ELISA). (3) Western blot assay was used to determine the serum levels of high-mobility group protein (HMGB1) in four mice of each group. (4) Ten mice in each group were used to measure serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), creatinine (CR) and blood urea nitrogen (BUN) by automatic biochemical analyzer. (5) After liver, lung and kidney tissues were fixed with formaldehyde, hematoxylin-eosin (HE) staining was performed (n=10 for each group). Results In DH5α group, 44102 group and 25922 group, bacteria, inflammatory cytokines TNF-α, IL-6 and HMGB1 protein, liver and kidney indicators ALT, AST, CR and BUN showed a sequential increasing trend (P＜0.01). The severe degrees of alveolar structure damage, hepatic cell infiltration and renal glomerular atrophy were DH5α group, 44102 group and 25922 group in turn. There were no obvious damages of lung, liver or kidney tissues in control group. Conclusion Escherichia coli 25922 induces severe sepsis injury and can be used to study the animal models of the initial inflammatory phase of sepsis. Escherichia coli 44102 induces moderate damage of sepsis and can be used in animal models that do not require definitive sepsis staging experiments. Escherichia coli DH5α induces less damage of sepsis and can be used to explore immunosuppressive therapy of the animal model of sepsis.

Survey and analysis on clinical engineering departments in Guangdong under new regulations / 医疗卫生装备

Objective To investigate the status quo of clinical engineering departments (CED) in Guangdong province, to find out the main problems and challenges, and to give some suggestions on promoting the development of clinical engineering. Methods Questionnaires were issued to directors or engineers in hospitals on department missions, staff composition, quality control and obstructive factors for discipline development. Statistical analysis was executed for the questionnaires. Results Only 53.19% of the CED operated independently. The daily CE practice in Guangdong hospitals included carrying out procurement, installation, maintenance and archiving. Only 28.0%of the hospitals had QC instruments. The education backgrounds were mainly restrained in undergraduate degree and junior college degree, accounting for 80.0%. Totally 39.0% of the clinical engineers majored in biomedical engineering. The personnel with primary or intermediate professional titles accounted for 61.96%. There was 0.68 engineer per 100 beds or 0.23 engineer per ten million Yuan medical equipment. The top 3 factors that hindered the development of CE were inadequacy of professional staff, low education level and absence of laws and regulations. Conclusion CED in Guangdong province drops behind the outstanding institutions in China, and has to be promoted with the efforts of supervision facilities and etc.

A New Species of Chigger Mite (Acari: Trombiculidae) from Rodents in Southwest China

This paper describes a new species of chigger mite (Acari: Trombiculidae), Gahrliepia cangshanensis n. sp., from rodents in southwest China. The specimens were collected from Yunnan red-backed voles, Eothenomys miletus (Thomas, 1914), and a Chinese white-bellied rat, Niviventer confucianus (Milne-Edwards, 1871) in Yunnan Province. The new species is unique mainly in its number of dorsal setae (n=21), and it has the following features: fT (formula of palpotarsus)=4B (B=branched), fp (formula of palpal seta)=B/N/N/N/B (N=naked), a broad tongue-shaped scutum with an almost straight posterior margin, and 17 PPLs (posterior posterolateral seta) with a length of 36-43 microm. This chigger mite may also infect other rodent hosts and may be distributed in other localities.