Undescribed polyketides from endophytes associated with the critically endangered conifer Abies beshanzuensis.

Four undescribed polyketides, beshanzones A (1) and B (2) as well as beshanhexanols A (3) and B (4), along with three known ones (5-7) were isolated from the rice fermentation of two endophytic fungi associated with the critically endangered Chinese endemic conifer Abies beshanzuensis. γ-Butyrolactone derivatives 1, 2, and 5 were isolated from Phomopsis sp. BSZ-AZ-2, an interesting strain that drawn our attention this time. The cyclohexanol derivatives 3, 4, 6 and 7 were obtained during a follow-up investigation on Penicillium commune BSZ-P-4-1. The chemical structures including absolute configurations of compounds 1-4 were determined by spectroscopic methods, Mo2(OAc)4 induced electronic circular dichroism (IECD), GIAO NMR calculations and DP4+ probability analyses. In particular, compound 2 contains a novel 5/5 bicyclic ring system, which might be biogenetically derived from the known compound 5 through hydrolysis followed by an Aldol reaction. All isolates were evaluated for their antimicrobial activities against a small panel of bacterial and fungal pathogens. Compounds 6 and 7 showed moderate inhibitory activities against Candida albicans, with MIC values of 16 and 32 µg/mL, respectively.

Salt Tolerance in Machilus faberi: Elucidating Growth and Physiological Adaptations to Saline Environments.

Adversity stress is the main environmental factor limiting plant growth and development, including salt and other stress factors. This study delves into the adaptability and salt tolerance mechanisms of Machilus faberi Hemsl, a species with potential for cultivation in salinized areas. We subjected the plants to various salt concentrations to observe their growth responses and to assess key physiological and biochemical indicators. The results revealed that under high salt concentrations (500 and 700 mmol-1/L), symptoms such as leaf yellowing, wilting, and eventual death were observed. Notably, plant height and shoot growth ceased on the 14th day of exposure. Chlorophyll content (a, b, total a + b, and the a/b ratio) initially increased but subsequently decreased under varying levels of salt stress. Similarly, the net photosynthetic rate, stomatal conductance, leaf water content, and root activity significantly declined under these conditions. Moreover, we observed an increase in malondialdehyde levels and relative conductivity, indicative of cellular damage and stress. The activity of superoxide dismutase and ascorbate peroxidase initially increased and then diminished with prolonged stress, whereas peroxidase activity consistently increased. Levels of proline and soluble protein exhibited an upward trend, contrasting with the fluctuating pattern of soluble sugars, which decreased initially but increased subsequently. In conclusion, M. faberi exhibits a degree of tolerance to salt stress, albeit with growth limitations when concentrations exceed 300 mmol-1/L. These results shed light on the plant's mechanisms of responding to salt stress and provide a theoretical foundation for its cultivation and application in salt-affected regions.

Bialorastins A-F, highly oxygenated and polycyclic andrastin-type meroterpenoids with proangiogenic activity from the deep-sea cold-seep-derived fungus Penicillium bialowiezense CS-283.

Six new highly oxygenated and polycyclic andrastin-type meroterpenoids, namely, bialorastins A-F (1-6), were discovered from the culture of Penicillium bialowiezense CS-283, a fungus isolated from the deep-sea cold seep squat lobster Shinkaia crosnieri. The planar structures and absolute configurations of these compounds were determined by detailed analysis of spectroscopic data, single crystal X-ray diffraction, and TDDFT-ECD calculations. Structurally, bialorastin A (1) represents a rare 17-nor-andrastin that possesses an unusual 2-oxaspiro[4.5]decane-1,4-dione moiety with a unique 6/6/6/6/5 polycyclic system, while bialorastin B (2) is also a 17-nor-andrastin featuring a gem-propane-1,2-dione moiety. Additionally, bialorastins C-E (3-5) possess a 6/6/6/6/5/5 fused hexacyclic skeleton, characterized by distinctive 3,23-acetal/lactone-bridged functionalities. All isolated compounds were evaluated for their proangiogenic activities in transgenic zebrafish. Compound 3 exhibited significant proangiogenic activity, which notably increased the number and length of intersegmental blood vessels in model zebrafish in a dose-dependent manner at concentrations of 20 and 40 µM. On a molecular scale, the tested compounds were modeled through molecular docking to have insight into the interactions with the possible target VEGFR2. Mechanistically, RT-qPCR results revealed that compound 3 could promote angiogenesis via activating VEGFR2 and subsequently activating the downstream PI3K/AKT and MAPK signaling pathways. These findings indicate that 3 could be a potential lead compound for developing angiogenesis agents.

Establishing an evaluation index system of nursing quality for clinical drug trials: A Delphi study.

AIMS: To construct a quality evaluation index system for clinical drug trials nursing management and obtain the weight of all indicators. DESIGN: A mixed-method research design with a quantitative component was used, primarily qualitative. METHODS: Through a literature review and semi-structured interview, an expert consultation questionnaire on the quality of nursing evaluation indicators for clinical drug trials was developed in April 2021. Eighteen experts in clinical drug trial nursing, medical, and pharmacy conducted 2 rounds of consultation according to the Delphi method to determine the indicators for evaluating the quality of clinical drug trial nursing. The weights of each indicator were determined using analytic hierarchical analysis. RESULTS: The established quality evaluation system of clinical drug trial nursing mainly includes 3 first-level indicators, 12 second-level indicators, and 59 third-level indicators. The positive coefficients of the two rounds of expert consultation were 90%-100%, and the authority coefficients were 0.831 and 0.885, respectively; the coordination coefficients were 0.189 and 0.214, respectively. The consulting results and weight settings are reliable. The evaluation index system we constructed is in line with the characteristics of the clinical drug trial nursing profession, with clear index levels and strong clinical operability, which can provide a reference for the assessment, monitoring and improvement of nursing quality in clinical drug trials. It will also clarify how nurses contribute to subjects' safety.

Natural products with 1,2-oxazine scaffold: occurrence, chemical diversity, bioactivity, synthesis, and biosynthesis.

Covering: up to the end of July, 20231,2-Oxazine is a heterocyclic scaffold rarely found in natural products and is characterized by a directly connected N-O bond in a six-membered ring. Since the discovery of geneserine, the first 1,2-oxazine-containing natural product (1,2-oxazine NP) being isolated from Calabar bean (Physostigma venenosum) in 1925, a total of 76 naturally occurring 1,2-oxazine NPs have been isolated and identified from various sources, which have attracted the attention of researchers in the field of natural product chemistry, organic synthesis, biosynthesis, and pharmacology. This review summarizes the chemical family of 1,2-oxazine NPs, focusing on their source organisms, structural diversities, chemical synthesis, and biosynthesis.

Antibacterial Indole Diketopiperazine Alkaloids from the Deep-Sea Cold Seep-Derived Fungus Aspergillus chevalieri.

A large body of fungal secondary metabolites has been discovered to exhibit potent antibacterial activities with distinctive mechanisms and has the potential to be an untapped resource for drug discovery. Here, we describe the isolation and characterization of five new antibacterial indole diketopiperazine alkaloids, namely 24,25-dihydroxyvariecolorin G (1), 25-hydroxyrubrumazine B (2), 22-chloro-25-hydroxyrubrumazine B (3), 25-hydroxyvariecolorin F (4), and 27-epi-aspechinulin D (5), along with the known analogue neoechinulin B (6) from a fungal strain of deep-sea cold seep-derived Aspergillus chevalieri. Among these compounds, 3 and 4 represented a class of infrequently occurring fungal chlorinated natural products. Compounds 1-6 showed inhibitory activities against several pathogenic bacteria with MIC values ranging from 4 to 32 µg/mL. It was revealed that compound 6 could induce structural damage to the Aeromonas hydrophila cells based on the observation by scanning electron microscopy (SEM), which led to the bacteriolysis and death of A. hydrophila, suggesting that neoechinulin B (6) might be a potential alternative to novel antibiotics development.

The predictive value of nontraditional lipid parameters for intracranial and extracranial atherosclerotic stenosis: a hospital-based observational study in China.

BACKGROUND: Ischemic strokes are primarily caused by intracranial and extracranial atherosclerotic stenosis. Nontraditional lipid parameters broaden traditional lipid profiles, better reflect the metabolism and interaction between different lipid components, and optimize the predictive ability of lipid profiles for atherosclerotic diseases. This research was carried out to investigate the predictive value of nontraditional lipid parameters for intracranial or extracranial atherosclerotic stenosis. METHODS: The investigation collected data from inpatients who underwent cervical vascular ultrasonography, carotid CTA, cerebral artery CTA or MRA, and brain MRI or CT from December 2014 to December 2021. The nontraditional lipid parameters were calculated by collecting traditional lipid parameters. To evaluate the predictive power of nontraditional lipid parameters, logistic regression and receiver operating characteristic curve (ROC) analyses were performed. RESULTS: Based on the inclusion and exclusion criteria, 545 patients were included. According to the imaging results, inpatients were divided into two groups, including no intracranial or extracranial atherosclerotic stenosis (n = 250) and intracranial or extracranial atherosclerotic stenosis (AS, n = 295). Among them, AS was further divided into three subgroups: intracranial atherosclerotic stenosis (ICAS), extracranial atherosclerotic stenosis (ECAS) and combined intracranial and extracranial atherosclerotic stenosis (IECAS). Logistic regression analysis showed that nontraditional lipid parameters, including the atherogenic index of plasma (AIP), TG/HDL-C, remnant cholesterol (RC), nonhigh-density lipoprotein cholesterol (non-HDL-C), lipoprotein combine index (LCI), atherogenic coefficient (AC), Castelli's index-I (CRI-I) and Castelli's index-II (CRI-II), were significantly correlated with intracranial or extracranial atherosclerotic stenosis (P < 0.05). Compared with other nontraditional lipid parameters, regardless of adjusting for potential confounding factors, AIP had a greater OR value in ICAS (OR = 4.226, 95% CI: 1.681-10.625), ECAS (OR = 2.993, 95% CI: 1.119-8.003) and IECAS (OR = 4.502, 95% CI: 1.613-12.561). ROC curve analysis revealed that nontraditional lipid parameters had good predictive power for intracranial or extracranial atherosclerotic stenosis. CONCLUSIONS: This Chinese hospital-based study demonstrates that nontraditional lipid parameters (AIP, LCI, RC, CRI-II, AC, CRI-I and non-HDL-C) are effective predictors of intracranial and extracranial atherosclerotic stenosis, of which AIP may be a significant risk factor for predicting atherosclerotic arterial stenosis in the intracranial or extracranial regions.

Plasmapheresis compared with conventional treatment for hypertriglyceridemia-induced acute pancreatitis: A systematic review and meta-analysis.

BACKGROUND: The treatment of acute pancreatitis (AP) induced by hypertriglyceridemia (HTG) remains controversial with regard to plasmapheresis vs conventional treatment. We reviewed relevant articles to explore the efficacy of plasmapheresis in the management of HTG-induced AP. METHODS: We systematically reviewed studies that compared plasmapheresis with conventional treatment for HTG-induced AP using three databases: PubMed, Embase, and Cochrane Library, as well as relevant references. The primary outcomes were 24 h triglyceride reduction rate and in-hospital mortality. RESULTS: A total of 791 articles were retrieved. Finally, 15 observational studies (1080 participants) were included, most of which were historical cohort studies. Compared with conventional treatment, plasmapheresis assisted in the reduction of serum triglyceride (TG) levels in the first 24 h after hospital admission (standardized mean difference [SMD]: 0.58; 95% confidence interval [CI]: 0.17 to 0.99; P = 0.005). However, it resulted in increased hospitalization costs (thousand yuan) (weighted mean difference [WMD]: 24.32; 95% CI: 12.96 to 35.68; P < 0.001). With regard to in-hospital mortality, although the mortality rate in the plasmapheresis group was higher than that in the conventional treatment group (relative risk [RR]: 1.74; 95% CI: 1.03 to 2.94; P = 0.038), the result was disturbed by confounding factors as per the subgroup and sensitivity analysis, as well as trial sequential analysis (TSA). No significant differences were found in other outcomes, including systematic complications, local complications, the requirement for surgery, and hospitalization duration. CONCLUSION: The effect of plasmapheresis in HTG-induced AP is not superior to that of conventional treatment, even resulting in a greater economic burden to patients and health care system. High quality randomized control trials are required to obtain a more a definitive understanding of this issue.

Comparative transcriptome analysis of leaf, stem, and root tissues of Semiliquidambar cathayensis reveals candidate genes involved in terpenoid biosynthesis.

BACKGROUND: Semiliquidambar cathayensis is a traditional medicinal plant and endemic species in China. Its roots, branches, leaves, bark, and nectar are known to have therapeutic effects against rheumatoid arthritis, lumbar muscle strain, and several other diseases. However, limited knowledge regarding the molecular properties of S. cathayensis highlights the need for further research in order to elucidate the underlying pathways governing the synthesis of its active ingredients and regulation of its accumulation processes. METHODS: We conducted transcriptome sequencing of the leaf, stem and root epidermises, and stem and root xylems of S. cathayensis with three biological replicates. Moreover, candidate genes involved in terpenoid biosynthesis, such as IDI, FPPS, DXR, SQS, GPPS, and HMGR were selected for quantitative real-time PCR analysis. RESULTS: We identified 88,582 unigenes. Among which, 36,144 unigenes were annotated to the nr protein database, 21,981 to the Gene Ontology database, 11,565 to the Clusters of Orthologous Groups database, 24,209 to the Pfam database, 21,685 to the SWISS-PROT database, and 12,753 to the Kyoto Encyclopedia of Genes and Genomes (KEGG), with 5072 unigenes common to all six databases. Of those annotated using the KEGG database, 187 unigenes were related to the terpenoid metabolism pathway, and expression analysis of the related genes indicated that the mevalonate and methylerythritol 4-phosphate pathways play different roles in terpenoid biosynthesis in different tissues of S. cathayensis. CONCLUSIONS: These findings greatly expand gene resources of S. cathayensis and provide basic data for the study of the biosynthetic pathways and molecular mechanisms of terpenoids.

The central nervous system control of energy homeostasis: High fat diet induced hypothalamic microinflammation and obesity.

Obesity is believed to arise through the imbalance of energy homeostasis controlled by the central nervous system, where the hypothalamus plays the fundamental role in energy metabolism. In this review, we will provide an overview regarding the functions of POMC neurons and AgRP neurons in acute nucleus of the hypothalamus which mediated the energy metabolism, highlighting their interactions with peripheral organs derived hormones in control of energy homeostasis. Furthermore, the role of high fat diet induced hypothalamic microinflammation in the pathogenesis of obesity will be discussed. We hope this review could help researchers to understand the mechanism of hypothalamus in control of energy metabolism, and design related drugs to block the pathways involving in the impaired metabolism in obese patients.

Chevalinulins A and B, Proangiogenic Alkaloids with a Spiro[bicyclo[2.2.2]octane-diketopiperazine] Skeleton from Deep-Sea Cold-Seep-Derived Fungus Aspergillus chevalieri CS-122.

Chevalinulins A (1) and B (2), two indole diketopiperazine alkaloids containing an unprecedented spiro[bicyclo[2.2.2]octane-diketopiperazine] skeleton, together with a known analogue neoechinulin B (3), were isolated from the deep-sea cold-seep-derived fungus Aspergillus chevalieri CS-122. Their structures were determined by spectroscopic analysis, single-crystal X-ray diffraction, specific rotation (SR), and NMR calculations. Compounds 1 and 2 exhibited significant in vivo proangiogenic activity in transgenic zebrafish.

A concise synthesis of herbertenolide.

A concise synthesis of (±)-herbertenolide has been accomplished herein. The strategy relies on a H2O2-mediated oxidative ring contraction of all-substituted cyclic α-formyl ketones for the stereospecific construction of contiguous quaternary carbon centers (CQCCs). Furthermore, a Sc(OTf)3/chiral N,N'-dioxide catalyzed asymmetric Michael addition of benzofuranone to MVK has been optimized for forging a chiral aromatic quaternary carbon center, which enables the formal synthesis of (+)-ent-herbertenolide.

EphA3 deficiency in the hypothalamus promotes high-fat diet-induced obesity in mice.

Erythropoietin-producing hepatocellular carcinoma A3 (EphA3) is a member of the largest subfamily of tyrosine kinase receptors-Eph receptors. Previous studies have shown that EphA3 is associated with tissue development. Recently, we have found that the expression of EphA3 is elevated in the hypothalamus of mice with diet-induced obesity (DIO). However, the role of EphA3 in hypothalamic-controlled energy metabolism remains unclear. In the current study, we demonstrated that the deletion of EphA3 in the hypothalamus by CRISPR/Cas9-mediated gene editing promotes obesity in male mice with high-fat diet feeding rather than those with normal chow diet feeding. Moreover, the deletion of hypothalamic EphA3 promotes high-fat DIO by increasing food intake and reducing energy expenditure. Knockdown of EphA3 leads to smaller intracellular vesicles in GT1-7 cells. The current study reveals that hypothalamic EphA3 plays important roles in promoting DIO.

Conservation of griseofulvin genes in the gsf gene cluster among fungal genomes.

The polyketide griseofulvin is a natural antifungal compound and research in griseofulvin has been key in establishing our current understanding of polyketide biosynthesis. Nevertheless, the griseofulvin gsf biosynthetic gene cluster (BGC) remains poorly understood in most fungal species, including Penicillium griseofulvum where griseofulvin was first isolated. To elucidate essential genes involved in griseofulvin biosynthesis, we performed third-generation sequencing to obtain the genome of P. griseofulvum strain D-756. Furthermore, we gathered publicly available genome of 11 other fungal species in which gsf gene cluster was identified. In a comparative genome analysis, we annotated and compared the gsf BGC of all 12 fungal genomes. Our findings show no gene rearrangements at the gsf BGC. Furthermore, seven gsf genes are conserved by most genomes surveyed whereas the remaining six were poorly conserved. This study provides new insights into differences between gsf BGC and suggests that seven gsf genes are essential in griseofulvin production.

Compound heterozygous pathogenic variants in the GALC gene cause infant-onset Krabbe disease.

BACKGROUND: Krabbe disease, also called globoid cell leukodystrophy, is an autosomal recessive disease caused by a deficiency of lysosomal galactocerebrosidase. Infantile Krabbe occurring before 12 months of age accounts for most cases. Typical clinical features include irritability, seizures, peripheral neuropathy, and progressive neurodegeneration. METHODS: We collected and summarized the clinical and genetic data of an 8-month-old boy who demonstrated Krabbe disease onset at around 6 months. Potential pathogenic variants were screened by whole exome sequencing, and effects of candidate variants on alternative transcript and truncated protein were further validated at the RNA and protein level. RESULTS: Galactocerebrosidase activity was nearly absent in his blood, and whole exome sequencing revealed compound heterozygous variants [NM_000153.4: (c.658C>T); (c.328+5G>T)] in galactosylceramidase (GALC). The variant c.328+5G>T was predicted to alter splicing, and the abnormal isoform transcript was validated by observation of abnormal RNA isoforms. The variant c.658C>T was predicted to cause truncation of the protein, which was validated by western blotting. CONCLUSIONS: Our findings revealed compound heterozygous variants with solid experimental results for Krabbe disease and provides strong evidence for further Krabbe disease screening and clinical consulting. As a rare inherited systemic disorder, genetic variants in Krabbe disease should be investigated, as experimental validation for clinical diagnosis is needed.

Six New Antimicrobial Metabolites from the Deep-Sea Sediment-Derived Fungus Aspergillus fumigatus SD-406.

Six new metabolites, including a pair of inseparable mixtures of secofumitremorgins A (1a) and B (1b), which differed in the configuration of the nitrogen atom, 29-hydroxyfumiquinazoline C (6), 10R-15-methylpseurotin A (7), 1,4,23-trihydroxy-hopane-22,30-diol (10), and sphingofungin I (11), together with six known compounds (2-5 and 8-9), were isolated and identified from the deep-sea sediment-derived fungus Aspergillus fumigatus SD-406. Their structures were determined by detailed spectroscopic analysis of NMR and MS data, chiral HPLC analysis of the acidic hydrolysate, X-ray crystallographic analysis, J-based configuration analysis, and quantum chemical calculations of ECD, OR, and NMR (with DP4+ probability analysis). Among the compounds, 1a/1b represent a pair of novel scaffolds derived from indole diketopiperazine by cleavage of the amide bond following aromatization to give a pyridine ring. Compounds 1, 4, 6, 7, 10 and 11 showed inhibitory activities against pathogenic bacteria and plant pathogenic fungus, with MIC values ranging from 4 to 64 µg/mL.

Lycopene Alleviates Hepatic Hypoxia/Reoxygenation Injury Through Nrf2/HO-1 Pathway in AML12 Cell.

[Figure: see text] Lycopene (lyc) has an effect on preventing cancer, yet its effects on hypoxia/reoxygenation (H/R) injury remained obscure. The study aimed at discovering its role in preventing hepatic cells against H/R injury. Hepatic cells were incubated in hypoxia incubator to simulate ischemia/reperfusion injury in vitro. Cell viability was detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay after Lycopene treatment with or without ML385 (nuclear factor erythroid 2-related factor 2 [Nrf2] inhibitor). Lactate dehydrogenase (LDH) and malondialdehyde (MDA) content were detected. Cellular cytokine (tumor necrosis factor-α, TNF-α; interleukin-6, IL-6) levels were measured using enzyme-linked immunosorbent assay (ELISA). Hepatic cell apoptosis and cellular reactive oxygen species (ROS) content was detected by flow cytometry. Nrf2 transfer was observed using immunofluorescence staining. Nrf2 and heme oxygenase-1 (HO-1) expressions were detected with quantitative real-time polymerase chain reaction and western blot as needed. In hepatic cells, after H/R, the viability was dropped, TNF-α and IL-6 levels and LDH and MDA content were increased, with high apoptosis rate and ROS content. Lycopene led to a reversed effect, with promotion on Nrf2 transfer from cytoplasm into nucleus and Nrf2/HO-1 pathway activation. Further experiments showed that ML385 could reverse the effects of Lycopene. Lycopene could activate Nrf2/HO-1 pathway to protect hepatic cells against H/R injury.

Hypothalamic extended synaptotagmin-3 contributes to the development of dietary obesity and related metabolic disorders.

The C2 domain containing protein extended synaptotagmin (E-Syt) plays important roles in both lipid homeostasis and the intracellular signaling; however, its role in physiology remains largely unknown. Here, we show that hypothalamic E-Syt3 plays a critical role in diet-induced obesity (DIO). E-Syt3 is characteristically expressed in the hypothalamic nuclei. Whole-body or proopiomelanocortin (POMC) neuron-specific ablation of E-Syt3 ameliorated DIO and related comorbidities, including glucose intolerance and dyslipidemia. Conversely, overexpression of E-Syt3 in the arcuate nucleus moderately promoted food intake and impaired energy expenditure, leading to increased weight gain. Mechanistically, E-Syt3 ablation led to increased processing of POMC to α-melanocyte-stimulating hormone (α-MSH), increased activities of protein kinase C and activator protein-1, and enhanced expression of prohormone convertases. These findings reveal a previously unappreciated role for hypothalamic E-Syt3 in DIO and related metabolic disorders.

Harmful chemicals of heat not burn product and its induced oxidative stress of macrophages at air-liquid interface: Comparison with ultra-light cigarette.

BACKGROUND: Harmful and potential harmful chemicals (HPHCs) and oxidative stress of macrophages are major factors responsible for smoking-caused chronic respiratory diseases. However, comparisons of HPHCs among heat not burn (HnB) product and ultra-light cigarette and their induced oxidative stress of macrophages have not been investigated. AIM: The study detected HPHCs deliveries from HnB and ultra-light and measured their induced oxidative stress of macrophages cultured at air-liquid interface (ALI). METHODS: Total particulate matter, tar and 28 chemicals delivered from HnB, ultra-light and 3R4F cigarettes were determined. Mouse mononuclear macrophages at ALI were exposed to the aerosol of three tobacco products. Cell viability was measured by MTT assay. Reduced glutathione was detected by colorimetry method. Reactive oxygen species (ROS) was determined by fluorescence method. RESULTS: The results showed levels of 26 common HPHCs from both HnB product and ultra-light cigarette were less than that from 3R4F cigarette. HnB product delivered formaldehyde, acetaldehyde, propanal, butyraldehyde and crotonaldehyde more than ultra-light cigarette. The levels of 21 HPHCs were lower in the HnB product compared to the ultra-light cigarette. At the same exposure dose and time, the order of cell viability induced by aerosol of that was HnB > ultra-light > 3R4F, the order of content of intracellular reduced glutathione induced by aerosol of that was HnB > ultra-light > 3R4F. It showed no significant difference of ROS level between ultra-light and HnB in each designed exposure dose. HnB induced more ROS than ultra-light cigarette in each designed exposure time. CONCLUSION: Conclusively, most HPHCs from HnB were lower than that from ultra-light, while certain harmful chemicals were higher than ultra-light, e.g., carbonyl compounds. HnB-induced oxidative stress of macrophages is less than ultra-light cigarette.

MRPL35 Is Up-Regulated in Colorectal Cancer and Regulates Colorectal Cancer Cell Growth and Apoptosis.

Mitochondrial ribosome proteins (MRPs), which are encoded by the nuclear genomic DNA, are important for mitochondrial-encoded protein synthesis and mitochondrial function. Emerging evidence suggests that several MRPs also exhibit important extra-mitochondrial functions, such as involvement in apoptosis, protein biosynthesis, and signal transduction. In this study, we demonstrate a significant role of MRP L35 (MRPL35) in colorectal cancer (CRC). The expression of MRPL35 was higher in CRC tissues than in matched cancer-adjacent tissues and higher in CRC cells than in normal mucosal epithelial cells. Higher MRPL35 expression in CRC tissue correlated with shorter overall survival for CRC patients. In vitro, down-regulation of MRPL35 led to increased production of reactive oxygen species (ROS) together with DNA damage, loss of cell proliferation, G2/M arrest, a decrease in mitochondrial membrane potential, apoptosis, and autophagy induction. MRPL35 knockdown inhibited tumor proliferation in a CRC xenograft nude mouse model. Furthermore, overexpression of MRPL35 or treatment of cells with the ROS scavenger, N-acetyl cysteine, abrogated ROS production, cell cycle arrest, and apoptosis in vitro. These findings suggest that MRPL35 plays an essential role in the development of CRC and may be a potential therapeutic target for CRC.