Understanding the role of exosomal lncRNAs in rheumatic diseases: a review.

Rheumatic diseases, a group of diseases whose etiology is still unclear, are thought to be related to genetic and environmental factors, leading to complex pathogenesis. Based on their multi-system involvement, the diagnosis and treatment continue to face huge challenges. Whole-genome assays provide a distinct direction for understanding the underlying mechanisms of such diseases. Exosomes, nano-sized bilayer membrane vesicles secreted by cells, are mentioned as a key element in the physiological and pathological processes of the body. These exosomes mediate biologically active substances, such as nucleic acids, proteins, and lipids and deliver them to cells. Notably, long non-coding RNAs (lncRNAs), a unique class of non-coding RNAs, have been implicated in the pathogenesis of rheumatic diseases. However, the mechanism needs to be further explored. This article provided a comprehensive review of the findings on exosomal lncRNAs in rheumatic diseases, including rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, autoimmune liver diseases, primary dermatomyositis, and systemic sclerosis. Through in-depth understanding of these lncRNAs and their involved signaling pathways provide new theoretical supports for the diagnosis and treatment of rheumatic diseases.

Resolution of herpes zoster-induced small bowel pseudo-obstruction by epidural nerve block: A case report.

BACKGROUND: When herpes zoster is complicated with paralytic ileus, this mostly involves acute intestinal pseudo-obstruction of Ogilvie's syndrome manifesting as obvious dilatation of the cecum and right colon; small intestinal obstruction is rare. Here, we present a patient with a very rare case of small bowel pseudo-obstruction. CASE SUMMARY: A 76-year-old female patient complained of right upper quadrant pain. Two days later, a blistering, right-sided rash of the thoracoabdominal dermatome (T5-T10) emerged in conjunction with small intestinal dilatation and the inability to defecate. Computed tomography of the abdomen confirmed small bowel pseudo-obstruction. Antiviral therapy, gastrointestinal decompression, and enemas proved unproductive. After 4 d of stagnation, an epidural block was performed for pain relief and prompted the passage of gas and stool, resolving the obstructive problem. Three days later, the rash appeared dry and crusted, and the pain diminished. After 5 d, no abnormality was visible by gastroenteroscopy, and the patient was discharged on day 7. CONCLUSION: This case shows that herpes zoster may induce small bowel pseudo-obstruction in addition to colonic pseudo-obstruction. Epidural block can not only treat intercostal neuralgia but also resolve small bowel pseudo-obstruction caused by herpes zoster.

Reprogramming the metabolism of Synechocystis PCC 6803 by regulating the plastoquinone biosynthesis.

Cyanobacteria can utilize CO2 or even N2 to produce a variety of high value-added products efficiently. Plastoquinone (PQ) is an important electron carrier in both of the photosynthetic and respiratory electron transport chain. Although the content of PQ, as well as their redox state, have an important effect on physiology and metabolism, there are relatively few studies on the synthesis of PQ and its related metabolic regulation mechanism in photosynthetic microorganisms. In this study, the strategies of overexpression of Geranyl diphosphate: 4-hydroxybenzoate geranyltransferase (lepgt) and addition of 4-hydroxybenzoate (4-HB) as the quinone ring precursor were adopted to regulate the biosynthesis of PQ in Synechocystis PCC 6803. Combined with the analysis the photosystem activity, respiration rate and metabolic components, we found the changes of intracellular PQ reprogrammed the metabolism of Synechocystis PCC 6803. The results showed that the overexpression of lepgt reduced PQ content dramatically, by 22.18%. Interestingly, both of the photosynthesis and respiration rate were enhanced. In addition, the intracellular lipid and protein contents were significantly increased. Whereas, the addition of low concentrations of 4-HB enhanced the biosynthesis of PQ, and the intracellular PQ contents were increased by 14.76%-70.86% in different conditions. Addition of 4-HB can regulate the photosystem efficiency and respiration and reprogram the metabolism of Synechocystis PCC 6803 efficiently. In a word, regulating the PQ biosynthesis provided a novel idea for promoting the reprogramming the physiology and metabolism of Synechocystis.

Grape seed procyanidin B2 promotes the autophagy and apoptosis in colorectal cancer cells via regulating PI3K/Akt signaling pathway.

Aim: Colorectal cancer (CRC) is a major malignancy in China, which is the critical risk of people health. Many natural herbs extracts have been found to exhibit good therapeutic effect on CRC. Our previous study found that grape seed procyanidins B2 (PB2) would induce CRC cell death. However, the molecular mechanism underlying its anti-tumor effect on CRC remains unclear. Thereby, this study aimed to investigate the anti-tumor mechanism of PB2 on CRC. Methods: CCK-8, western blotting, flow cytometry, qRT-PCR and animal study were used in the current study. Results: The in vitro and in vivo data demonstrated that PB2 could promote the apoptosis of CRC cells in a dose-dependent manner, which was significantly reversed by caspase 3 inhibitor. Meanwhile, PB2 dose-dependently induced autophagy in CRC cells, which was markedly attenuated by autophagy inhibitor 3-MA. In addition, PB2 dose-dependently inhibited the expressions of p-PI3K, p-Akt and p-mTOR in the cells. Conclusion: PB2 dose-dependently induced apoptosis and autophagy in CRC cells via downregulation of PI3K/Akt pathway. This study provided the experimental basis for further development of PB2 as a new effective anticancer drug for the patients with CRC.

Atractylenolide II reverses the influence of lncRNA XIST/miR-30a-5p/ROR1 axis on chemo-resistance of colorectal cancer cells.

This investigation was conducted to elucidate whether atractylenolide II could reverse the role of lncRNA XIST/miR-30a-5p/ROR1 axis in modulating chemosensitivity of colorectal cancer cells. We totally collected 294 pairs of colorectal cancer tissues and adjacent normal tissues and also purchased colorectal cancer cell lines and human embryonic kidney cell line. 5-fluorouracil, cisplatin, mitomycin and adriamycin were designated as the chemotherapies for colorectal cell lines, and atractylenolides were arranged as the Chinese drug. The expressions of XIST, miR-30a-5p and ROR1 were quantified with aid of qRT-PCR or Western blot, and luciferase reporter gene assay was implemented to determine the relationships among XIST, miR-30a-5p and ROR1. Our results demonstrated that XIST and ROR1 expressions were dramatically up-regulated, yet miR-30a-5p expression was down-regulated within colorectal cancer tissues (P < 0.05). The overexpressed XIST and ROR1, as well as under-expressed miR-30a-5p, were inclined to promote viability and proliferation of colorectal cells under the influence of chemo drugs (P < 0.05). In addition, XIST could directly target miR-30a-5p, and ROR1 acted as the targeted molecule of miR-30a-5p. Interestingly, atractylenolides not only switched the expressions of XIST, miR-30a-5p and ROR1 within colorectal cancer cells but also significantly intensified the chemosensitivity of colorectal cancer cells (P < 0.05). Finally, atractylenolide II was discovered to slow down the viability and proliferation of colorectal cancer cells (P < 0.05). In conclusion, the XIST/miR-30a-5p/ROR1 axis could be deemed as pivotal markers underlying colorectal cancer, and administration of atractylenolide II might improve the chemotherapeutic efficacy for colorectal cancer.

Comparative transcriptome analyses of oleaginous Botryococcus braunii race A reveal significant differences in gene expression upon cobalt enrichment.

BACKGROUND: Botryococcus braunii is known for its high hydrocarbon content, thus making it a strong candidate feedstock for biofuel production. Previous study has revealed that a high cobalt concentration can promote hydrocarbon synthesis and it has little effect on growth of B. braunii cells. However, mechanisms beyond the cobalt enrichment remain unknown. This study seeks to explore the physiological and transcriptional response and the metabolic pathways involved in cobalt-induced hydrocarbon synthesis in algae cells. RESULTS: Growth curves were similar at either normal or high cobalt concentration (4.5 mg/L), suggesting the absence of obvious deleterious effects on growth introduced by cobalt. Photosynthesis indicators (decline in Fv/Fm ratio and chlorophyll content) and reactive oxygen species parameters revealed an increase in physiological stress in the high cobalt concentration. Moreover, cobalt enrichment treatment resulted in higher crude hydrocarbon content (51.3% on day 8) compared with the control (43.4% on day 8) throughout the experiment (with 18.2% improvement finally). Through the de novo assembly and functional annotation of the B. braunii race A SAG 807-1 transcriptome, we retrieved 196,276 non-redundant unigenes with an average length of 1086 bp. Of the assembled unigenes, 89,654 (45.7%), 42,209 (21.5%), and 32,318 (16.5%) were found to be associated with at least one KOG, GO, or KEGG ortholog function. In the early treatment (day 2), the most strongly upregulated genes were those involved in the fatty acid biosynthesis and metabolism and oxidative phosphorylation, whereas the most downregulated genes were those involved in carbohydrate metabolism and photosynthesis. Genes that produce terpenoid liquid hydrocarbons were also well identified and annotated, and 21 (or 29.2%) were differentially expressed along the cobalt treatment. CONCLUSIONS: Botryococcus braunii SAG 807-1 can tolerate high cobalt concentration and benefit from hydrocarbon accumulation. The time-course expression profiles for fatty acid biosynthesis, metabolism, and TAG assembly were obtained through different approaches but had equally satisfactory results with the redirection of free long-chain fatty acid and VLCFA away from TAG assembly and oxidation. These molecules served as precursors and backbone supply for the fatty acid-derived hydrocarbon accumulation. These findings provide a foundation for exploiting the regulation mechanisms in B. braunii race A for improved photosynthetic production of hydrocarbons.

Genotyping and drug-resistance epidemiology of mycobacterium tuberculosis in Xuzhou, China.

BACKGROUND: To explore the genetic diversity and drug resistance status of MTB in Xuzhou, China. METHODS: A total of 325 clinical MTB strains were genotyped by spacer-oligonucleotide typing (spoligotyping) and mycobacterial interspersed repetitive unit variable number of tandem repeats (MIRU-VNTR). Phenotypic resistance was assessed by drug susceptibility testing (DST). RESULT: Based on the spoligotyping method, 325 MTB isolates were classified into 5 known genotypes and 12 unknown genotypes, and the largest branch comprised 268 strains belonging to the Beijing family. Based on the 15-loci VNTR typing method, 325 MTB isolates were divided into 35 clusters and 220 unique patterns. Compared to the low discriminatory power of spoligotyping genotyping (HGDI = 0.3444), 15-loci VNTR genotyping had a significantly higher discriminatory power for all strains (HGDI = 0.9980), particularly for the Beijing family strains (HGDI = 0.9892). When spoligotyping and 15-loci VNTR methods were used together, the discriminatory power increased to 0.9991. The Beijing family strain presented increased risks for developing multi-drug resistance TB (P < 0.05). CONCLUSION: The Beijing family isolates is the most prevalent strains in Xuzhou. Spoligotyping, in combination with 15-loci MIRU-VNTR, is useful for epidemiological analysis of MTB transmission in Xuzhou.

Ultrastructural and proteomic alteration of superficial masseter muscle after lower jaw sagittal advancement in rat.

OBJECTIVE: The purpose of this study was to investigate the ultrastructural and proteomic alteration of the superficial masseter muscle (SM) after lower jaw sagittal advancement in a rat model. METHODS: Six 35-day-old male Sprague-Dawley rats were utilized in a transmission electron microscopy study, and six more in a proteomic study. The rats were randomly allocated to two experimental and two control groups (n=3). The experimental groups were fitted with fixed devices that protruded the mandible, whereas the control groups were not fitted with the devices. The rats were sacrificed 3 days after mandibular advancement. Transmission electron microscopy analysis, Western blot analysis, comparative proteomic analysis, and matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry (MS) were applied to profile qualitative and quantitative differences in the morphology and proteome of rat SM. RESULTS: Under the transmission electron microscope, morphological changes of the SM were associated with deregulation of the myofibrillar network accompanied by fibre rupture, interlaced myofilaments, and changes in the mitochondria and sarcoplasmic reticulum cisternae. The shape of mitochondria changed. Proteomic analysis identified fourteen differentially expressed proteins involved in metabolism, contraction or the cytoskeleton, and transport. Amongst these, the expression of 13 proteins increased and 1 decreased. According to Western blot analysis, myosin heavy chain II was down-regulated. CONCLUSION: Three days after functional mandibular advancement, the ultrastructure of rat SM had changed. This change paralleled changes in metabolic, contractile and cytoskeletal, and transport proteins, which affected SM physiology. The energy metabolism of SM increased, and the muscle velocity and force of contraction decreased.

Quantitation of HBV covalently closed circular DNA in micro formalin fixed paraffin-embedded liver tissue using rolling circle amplification in combination with real-time PCR.

BACKGROUND: The study aimed to develop an effective method to quantitate HBV covalently closed circular DNA (cccDNA) using small section of formalin fixed paraffin-embedded (FFPE) liver biopsy. METHODS: Plasmid-safe ATP-dependent DNase (PSAD)-treated samples were subjected to rolling circle amplification (RCA) prior to real-time PCR mediated by cccDNA-selective primers. Human beta-actin gene was used as a reference control. RESULTS: Compared to the classical method, i.e., PSAD digestion+real-time PCR, introduction of RCA increased the lower limit of detection for about 2 logs with good inter- and intra-assay reproducibility. HBV cccDNA was detected in 91.5% (119/130) of the FFPE samples. The cccDNA levels (copy/cell) between FFPE liver tissues and fresh frozen counterpart tissues were comparable. The median of cccDNA level in HBeAg-positive patients was higher than that in HBeAg-negative ones (52.60 vs. 31.25copies/cell, P<0.01). Intrahepatic cccDNA level was positively correlated with intrahepatic HBV total DNA level, but not obviously correlated with serum HBV DNA or alanine aminotransferase levels. CONCLUSIONS: The method could sensitively and specifically quantitate intrahepatic HBV cccDNA in micro FFPE liver biopsy tissue for evaluation of HBV replication status in the liver.