Curriculum vitae of CUG binding protein 1 (CELF1) in homeostasis and diseases: a systematic review.

RNA-binding proteins (RBPs) are kinds of proteins with either singular or multiple RNA-binding domains (RBDs), and they can assembly into ribonucleic acid-protein complexes, which mediate transportation, editing, splicing, stabilization, translational efficiency, or epigenetic modifications of their binding RNA partners, and thereby modulate various physiological and pathological processes. CUG-BP, Elav-like family 1 (CELF1) is a member of the CELF family of RBPs with high affinity to the GU-rich elements in mRNA, and thus exerting control over critical processes including mRNA splicing, translation, and decay. Mounting studies support that CELF1 is correlated with occurrence, genesis and development and represents a potential therapeutical target for these malignant diseases. Herein, we present the structure and function of CELF1, outline its role and regulatory mechanisms in varieties of homeostasis and diseases, summarize the identified CELF1 regulators and their structure-activity relationships, and prospect the current challenges and their solutions during studies on CELF1 functions and corresponding drug discovery, which will facilitate the establishment of a targeted regulatory network for CELF1 in diseases and advance CELF1 as a potential drug target for disease therapy.

Young Sca-1+ bone marrow stem cell-derived exosomes preserve visual function via the miR-150-5p/MEKK3/JNK/c-Jun pathway to reduce M1 microglial polarization.

BACKGROUND: Polarization of microglia, the resident retinal immune cells, plays important roles in mediating both injury and repair responses post-retinal ischemia-reperfusion (I/R) injury, which is one of the main pathological mechanisms behind ganglion cell apoptosis. Aging could perturb microglial balances, resulting in lowered post-I/R retinal repair. Young bone marrow (BM) stem cell antigen 1-positive (Sca-1+) cells have been demonstrated to have higher reparative capabilities post-I/R retinal injury when transplanted into old mice, where they were able to home and differentiate into retinal microglia. METHODS: Exosomes were enriched from young Sca-1+ or Sca-1- cells, and injected into the vitreous humor of old mice post-retinal I/R. Bioinformatics analyses, including miRNA sequencing, was used to analyze exosome contents, which was confirmed by RT-qPCR. Western blot was then performed to examine expression levels of inflammatory factors and underlying signaling pathway proteins, while immunofluorescence staining was used to examine the extent of pro-inflammatory M1 microglial polarization. Fluoro-Gold labelling was then utilized to identify viable ganglion cells, while H&E staining was used to examine retinal morphology post-I/R and exosome treatment. RESULTS: Sca-1+ exosome-injected mice yielded better visual functional preservation and lowered inflammatory factors, compared to Sca-1-, at days 1, 3, and 7 days post-I/R. miRNA sequencing found that Sca-1+ exosomes had higher miR-150-5p levels, compared to Sca-1- exosomes, which was confirmed by RT-qPCR. Mechanistic analysis found that miR-150-5p from Sca-1+ exosomes repressed the mitogen-activated protein kinase kinase kinase 3 (MEKK3)/JNK/c-Jun axis, leading to IL-6 and TNF-α downregulation, and subsequently reduced microglial polarization, all of which contributes to reduced ganglion cell apoptosis and preservation of proper retinal morphology. CONCLUSION: This study elucidates a potential new therapeutic approach for neuroprotection against I/R injury, via delivering miR-150-5p-enriched Sca-1+ exosomes, which targets the miR-150-5p/MEKK3/JNK/c-Jun axis, thereby serving as a cell-free remedy for treating retinal I/R injury and preserving visual functioning.

Autophagy gene Atg7 regulates the development of radiation-induced skin injury and fibrosis of skin.

BACKGROUND: Radiation-induced skin injury, which may progress to fibrosis, is a severe side effect of radiotherapy in patients with cancer. However, currently, there is a lack of preventive or curative treatments for this injury. Meanwhile, the mechanisms underlying this injury remain poorly understood. Here, we elucidated whether autophagy is essential for the development of radiation-induced skin injury and the potential molecular pathways and mechanisms involved. METHODS AND RESULTS: We used the myofibroblast-specific Atg7 knockout (namely, conditional Atg7 knockout) mice irradiated with a single electron beam irradiation dose of 30 Gy. Vaseline-based 0.2% rapamycin ointment was topically applied once daily from the day of irradiation for 30 days. On day 30 post irradiation, skin tissues were harvested for further analysis. In vitro, human foreskin fibroblast cells were treated with rapamycin (100 nM) for 24 h and pretreated with 3-MA (5 mM) for 12 h. Macroscopic skin manifestations, histological changes, and fibrosis markers at the mRNA and protein expression levels were measured. Post irradiation, the myofibroblast-specific autophagy-deficient (Atg7Flox/Flox Cre+ ) mice had increased fibrosis marker (COL1A1, CTGF, TGF-ß1, and α-SMA) levels in the irradiated area and had more severe macroscopic skin manifestations than the control group (Atg7Flox/Flox Cre- ) mice. Treatment with an autophagy agonist rapamycin attenuated macroscopic skin injury scores and skin fibrosis marker levels with decreased epidermal thickness and dermal collagen deposition in Atg7Flox/Flox Cre+ mice compared with the vehicle control. Moreover, in vitro experiment results were consistent with the in vivo results. Together with studies at the molecular level, we found that these changes involved the Akt/mTOR pathway. In addition, this phenomenon might also relate to Nrf2-autophagy signaling pathway under oxidative stress conditions. CONCLUSION: In conclusion, Atg7 and autophagy-related mechanisms confer radioprotection, and reactivation of the autophagy process can be a novel therapeutic strategy to reduce and prevent the occurrence of radiodermatitis, particularly skin fibrosis, in patients with cancer.

miR-199b-3p contributes to acquired resistance to cetuximab in colorectal cancer by targeting CRIM1 via Wnt/ß-catenin signaling.

BACKGROUND: Despite advances in the development of efficient chemotherapy, the treatment of colorectal cancer (CRC) remains a challenge due to acquired chemoresistance. It has been reported that microRNAs (miRNAs) dysregulation is associated with the development of chemoresistance. Recently, the expression of miR-199b-3p has been found to be significantly different between cetuximab (CTx)-resistant and -sensitive CRC cells. However, its role and the underlying mechanisms in acquired chemoresistance to CTx in CRC are still obscure. METHODS: Here we report that miR-199b-3p is significantly up-regulated in both CTx-resistant (CTxR) CRC tissues and cell lines. RESULTS: Functional assays showed that suppressing miR-199b-3p could improve the sensitivity of CRC-CTxR cells to CTx, thereby reducing cell proliferation, migration and invasion, and enhancing cell apoptosis. Mechanistic studies revealed that CRIM1 is a direct target of miR-199b-3p in CRC-CTxR cells; and the effect of miR-199b-3p on CTx-resistance was exerted by regulating the Wnt/ß-catenin signaling pathway via CRIM1. Furthermore, mice xenograft models were established and confirmed that down-regulating miR-199b-3p restores the inhibition effect of CTx on tumor growth in CRC-CTxR. Collectively, our data suggest that silencing miR-199b-3p could enhance the anti-tumor effects of CTx on CTx-resistant CRC in vitro and in vivo by activating Wnt/ß-catenin signaling via the down-regulation of CRIM1. CONCLUSIONS: Our findings suggest miR-199b-3p might serve as a promising therapeutic target against CTx resistant CRC, and provide scientific information for exploring novel strategies of improving the efficacy of CTx for CRC patients.

Association between Mycobacterium tuberculosis genotype and diabetes mellitus/hypertension: a molecular study.

BACKGROUND: A paucity of studies focused on the genetic association that tuberculosis (TB) patients with non-communicable diseases (NCDs) are more likely to be infected with Mycobacterium tuberculosis (MTB) with more potent virulence on anti-TB drug resistance than those without NCDs. The study aimed to document the predominant genotype, determine the association between MTB genotypes and NCD status and drug resistance. METHODS: We conducted a molecular study in 105 TB patients based on a cross-sectional study focused on the comorbid relationship between chronic conditions and TB among 1773 subjects from September 1, 2019 to August 30, 2020 in Guizhou, China. The participants were investigated through face-to-face interviews, followed by NCDs screening. The DNA of MTB isolates was extracted prior to genotyping using 24 loci MIRU-VNTR. The subsequent evaluations were performed by phylogenetic trees, combined with tests of statistical power, Chi-square or Fisher and multivariate logistic regression analysis. RESULTS: The Beijing family of Lineage 2 (East Asia) was the predominant genotype accounting for 43.8% (46/105), followed by Lineage 4 (Euro-America) strains, including Uganda I (34.3%, 36/105), and the NEW-1 (9.5%, 10/105). The proportion of Beijing strain in patients with and without NCDS was 28.6% (8/28) and 49.4% (38/77), respectively, with a statistical power test value of 24.3%. No significant association was detected between MTB genotype and NCD status. A low clustering rate (2.9%) was identified, consisting of two clusters. The rates of global, mono-, poly- and multi-drug resistance were 16.2% (17/105), 14.3% (15/105), 1.0% (1/105) and 4.8% (5/105), respectively. The drug-resistant rates of rifampicin, isoniazid, and streptomycin, were 6.7% (7/105), 11.4% (12/105) and 5.7% (6/105), respectively. Isoniazid resistance was significantly associated with the Beijing genotype of Lineage 2 (19.6% versus 5.1%). CONCLUSIONS: The Lineage 2 East Asia/Beijing genotype is the dominant genotype of the local MTB with endogenous infection preponderating. Not enough evidence is detected to support the association between the MTB genotype and diabetes/hypertension. Isoniazid resistance is associated with the Lineage 2 East Asia/Beijing strain.

Coptidis Rhizoma: a comprehensive review of its traditional uses, botany, phytochemistry, pharmacology and toxicology.

CONTEXT: Coptidis rhizome (CR), also known as Huanglian in Chinese, is the rhizome of Coptis chinensis Franch., C. deltoidea C.Y. Cheng et Hsiao, or C. teeta Wall (Ranunculaceae). It has been widely used to treat bacillary dysentery, diabetes, pertussis, sore throat, aphtha, and eczema in China. OBJECTIVES: The present paper reviews the latest advances of CR, focusing on the botany, phytochemistry, traditional usages, pharmacokinetics, pharmacology and toxicology of CR and its future perspectives. METHODS: Studies from 1985 to 2018 were reviewed from books; PhD. and MSc. dissertations; the state and local drug standards; PubMed; CNKI; Scopus; the Web of Science; and Google Scholar using the keywords Coptis, Coptidis Rhizoma, Huanglian, and goldthread. RESULTS: Currently, 128 chemical constituents have been isolated and identified from CR. Alkaloids are the characteristic components, together with organic acids, coumarins, phenylpropanoids and quinones. The extracts/compounds isolated from CR cover a wide pharmacological spectrum, including antibacterial, antivirus, antifungal, antidiabetic, anticancer and cardioprotective effects. Berberine is the most important active constituent and the primary toxic component of CR. CONCLUSIONS: As an important herbal medicine in Chinese medicine, CR has the potential to treat various diseases. However, further research should be undertaken to investigate the clinical effects, toxic constituents, target organs and pharmacokinetics, and to establish criteria for quality control, for CR and its related medications. In addition, the active constituents, other than alkaloids, in both raw and processed products of CR should be investigated.

[Spectrum-effect relationship between HPLC fingerprint and free radicals scavenging in Guizhi Shaoyao Zhimu Decoction].

To establish the spectrum-effect relationship between HPLC fingerprint and free radicals activity scavenging in Guizhi Shaoyao Zhimu Decoction( GSZD),and provide a basis for the quality evaluation and modernization of classical prescriptions. Shimadsu GL-science C18 column( 4. 6 mm×250 mm,5 µm) was used with acetonitrile-0. 1% formic acid solution as the mobile phase for gradient elution. The detective wave length was 254 nm; the column temperature was set at 32 ℃; the injection volume was 20 µL; and the flow rate was 1. 0 m L·min-1.10 batches of primary standard samples of GSZD were detected,and their HPLC fingerprint was established by using the similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine( TCM). The activity of scavenging free radicals was studied by 1,1-diphenyl-2-trinitrophenylhydrazine( DPPH) method,and the spectrum-effect relationship was studied by Pearson bivariate correlation analysis. The common mode of GSZD fingerprints was established,and 26 common peaks were marked,with similarities ranging from 0. 929 to 0. 998. Eight of the chromatographic peaks were identified by using the control comparison method: gallic acid,mangiferin,paeoniflorin,glycyrrhizin,asparagus,5-O-methylvisamicin,cinnamic acid,and ammonium glycyrrhetate. Among them,the content changes of No. 14( paeoniside),20,12( mangiferin),13 and 23( cinnamic acid) common peaks were negatively correlated with free radical scavenging activity. The fingerprint showed high precision,repeatability and stability,and the common peaks were well separated,so it can be used for the quality evaluation of GSZD,and could provide reference for further studies on the material basis of GSZD.

Association Between Body Weight Change Before and After Delivery and Development of Nonmetabolic Syndrome: A Prospective Study.

The aim of the work was to investigate the association between body weight change before and after delivery and development of nonmetabolic syndrome in Chinese females aged ≥40 years. We selected 789 participants without metabolic syndrome randomly from a baseline survey performed in Luzhou, China in 2011. We took the group with decreasing or no increasing body mass index difference during a pregnancy as "R-Body Mass Index 1" (n=286) and divided the group with increasing body mass index difference during a pregnancy into "R-Body Mass Index 2" (n=254) and "R-Body Mass Index 3" (n=249) based upon P50. All study participants were followed up every year, and a questionnaire, physical examination, and biochemical detection were administered after 3 years. Of 789 participants, 82 nonmetabolic syndrome women developed metabolic syndrome during 3-year follow-up. The morbidity of metabolic syndrome in the R-BMI1, R-BMI2, and R-BMI3 groups was 5.2%, 11.8%, and 14.9%, respectively. Compared to the R-BMI1 group, the relative risk for R-BMI2 was 1.92 (95% confidence interval: 1.03-3.58, p=0.040) and for R-BMI3 was 2.20 (95% confidence interval: 1.20-4.03, p=0.011). After adjusting for age, BMI, WHR, baseline blood glucose, HbA1c, TG, HDL-C, SBP, DBP, age of menarche and menopause, and delivery times, the relative risks were similar to the unadjusted relative risks. In conclusion, body weight change after delivery was associated with metabolic syndrome: the higher the weight gain, the higher the risk of metabolic syndrome.

The mitochondrial permeability transition pore regulates endothelial bioenergetics and angiogenesis.

RATIONALE: The mitochondrial permeability transition pore is a well-known initiator of cell death that is increasingly recognized as a physiological modulator of cellular metabolism. OBJECTIVE: We sought to identify how the genetic deletion of a key regulatory subunit of the mitochondrial permeability transition pore, cyclophilin D (CypD), influenced endothelial metabolism and intracellular signaling. METHODS AND RESULTS: In cultured primary human endothelial cells, genetic targeting of CypD using siRNA or shRNA resulted in a constitutive increase in mitochondrial matrix Ca(2+) and reduced nicotinamide adenine dinucleotide (NADH). Elevated matrix NADH, in turn, diminished the cytosolic NAD(+)/NADH ratio and triggered a subsequent downregulation of the NAD(+)-dependent deacetylase sirtuin 1 (SIRT1). Downstream of SIRT1, CypD-deficient endothelial cells exhibited reduced phosphatase and tensin homolog expression and a constitutive rise in the phosphorylation of angiogenic Akt. Similar changes in SIRT1, phosphatase and tensin homolog, and Akt were also noted in the aorta and lungs of CypD knockout mice. Functionally, CypD-deficient endothelial cells and aortic tissue from CypD knockout mice exhibited a dramatic increase in angiogenesis at baseline and when exposed to vascular endothelial growth factor. The NAD(+) precursor nicotinamide mononucleotide restored the cellular NAD(+)/NADH ratio and normalized the CypD-deficient phenotype. CypD knockout mice also presented accelerated wound healing and increased neovascularization on tissue injury as monitored by optical microangiography. CONCLUSIONS: Our study reveals the importance of the mitochondrial permeability transition pore in the regulation of endothelial mitochondrial metabolism and vascular function. The mitochondrial regulation of SIRT1 has broad implications in the epigenetic regulation of endothelial phenotype.

Association between serum gamma-glutamyl transferase and serum uric acid levels in Chinese females: A cross-sectional study.

OBJECTIVE: To investigate the association between serum gamma-glutamyl transferase (GGT) levels and serum uric acid levels in middle-aged and elderly Chinese females. METHODS: A cross-sectional population survey was performed in Luzhou, China (2014). Questionnaires, physical examinations and biochemical tests were conducted. Finally, we included 2486 females who were > 40 years old as participants. Multiple linear regression analysis was used to estimate the association of serum acid levels and other variables. Serum GGT levels were divided into four groups using the 25th, 50th and 75th percentiles as cut-off points. Finally, binary logistic regression analysis was used to investigate the association of different serum GGT quartiles with the risk of hyperuricemia. RESULTS: The prevalence of hyperuricemia was 25.1% in the studied population and gradually increased across the serum GGT quartiles (P < 0.05). Binary logistic regression analysis showed that compared with subjects in the lowest quartile of serum GGT levels, the adjusted odds ratio (ORs) for uric acid in the highest quartile was 2.34 (95% confidence interval (CI), 1.68-3.28, P < 0.001),after corrections for TG, TC, HDL-C, LDL-C, creatinine (CR), GGT, AST, ALT, fasting plasma glucose (FPG), postprandial 2-h plasma glucose, hemoglobin A1c(HbA1c), age, BMI, SBP, DBP, waist-to-hip ratio and neck circumference (NC). CONCLUSIONS: The serum GGT level is associated with hyperuricemia in middle-aged and elderly Chinese females.

Assessment of edema volume in skin upon injury in a mouse ear model with optical coherence tomography.

Accurate measurement of edema volume is essential for the investigation of tissue response and recovery following a traumatic injury. The measurements must be noninvasive and repetitive over time so as to monitor tissue response throughout the healing process. Such techniques are particularly necessary for the evaluation of therapeutics that are currently in development to suppress or prevent edema formation. In this study, we propose to use optical coherence tomography (OCT) technique to image and quantify edema in a mouse ear model where the injury is induced by a superficial-thickness burn. Extraction of edema volume is achieved by an attenuation compensation algorithm performed on the three-dimensional OCT images, followed by two segmentation procedures. In addition to edema volume, the segmentation method also enables accurate thickness mapping of edematous tissue, which is an important characteristic of the external symptoms of edema. To the best of our knowledge, this is the first method for noninvasively measuring absolute edema volume.

4D optical coherence tomography-based micro-angiography achieved by 1.6-MHz FDML swept source.

We demonstrate the use of an ultra-high-speed swept-source optical coherence tomography (OCT) to achieve optical micro-angiography (OMAG) of microcirculatory tissue beds in vivo. The system is based on a 1310-nm Fourier domain mode-locking (FDML) laser with 1.6-MHz A-line rate, providing a frame rate of 3.415 KHz, an axial resolution of ∼10 µm and signal to noise ratio of 102 dB. Motion from blood flow causes change in OCT signals between consecutive B-frames acquired at the same location. Intensity-based inter-frame subtraction algorithm is applied to extract blood flow from tissue background without any motion correction. We demonstrate the capability of this 1.6-MHz OCT system for 4D OMAG of in vivo tissue at a volume rate of 4.7 volumes/s (volume size: 512×200×720 voxels).

Lymphatic response to depilation-induced inflammation in mouse ear assessed with label-free optical lymphangiography.

BACKGROUND AND OBJECTIVES: Optical microangiography (OMAG) is a noninvasive technique capable of imaging 3D microvasculature. OMAG-based optical lymphangiography has been developed for 3D visualization of lymphatic vessels without the need for exogenous contrast agents. In this study, we utilize the optical lymphangiography to investigate dynamic changes in lymphatic response within skin tissue to depilation-induced inflammation by using mouse ear as a simple tissue model. MATERIALS AND METHODS: A spectral-domain optical coherence tomography (OCT) system is used in this study to acquire volumetric images of mouse ear. The system operates under the ultrahigh-sensitive OMAG scanning protocol with five repetitions for each B frame. An improved adaptive-threshold-based method is proposed to segment lymphatic vessels from OCT microstructure images. Depilation is achieved by placing hair removal lotion on mouse ear pinna for 5 minutes. Three acquisitions are made before depilation, 3-minute and 30-minute post-depilation, respectively. RESULTS: Right after the application of depilation lotion on the skin, we observe that the blind-ended sacs of initial lymphatics are mainly visible in a specific area of the normal tissue. At 5 minutes, more collecting lymphatic vessels start to form, evidenced by their valve structure that only exists in collecting lymphatic vessels. The lymphangiogenesis is almost completed within 8 minutes in the inflammatory tissue. CONCLUSIONS: Our experimental results demonstrate that the OMAG-based optical lymphangiography has great potential to improve the understanding of lymphatic system in response to various physiological conditions, thus would benefit the development of effective therapeutics.

[Study on change rule of 6 ester-type alkaloids in process of Heishunpian].

To study the variation of six ester-type alkaloids and characteristic fingerprints in the process from Radix Aconite Lateralis to Heishunpian and lay a foundation for the study of the processing principle of Heishunpian, HPLC. analysis was performed on a Phenomenex Gemini C18 (4.6 mm x 250 mm, 5 microm) with acetonitrile and 40 mmol x L(-1) ammonium acetate (adjusted to pH 10 with concentrated ammonia water) as mobile phase. The detection wavelength was set at 235 nm. The flow rate was set at 0.8 mL x min(-1) and the injection volume was 10-20 microL. Six ester-type alkaloids were determined and characteristic fingerprints of the process were established. As the process continues, the contents of diester diterpene alkaloids were decreased step by step, while the contents varia tion of monoester diterpene alkaloids were not obvious. Each sample showed significant difference in characteristic fingerprints. With the exception of 6 known monoester diterpene alkaloids and diester diterpene alkaloids, 13 peaks were marked in the characteristic fingerprints, of which the total change rule of the other 7 unknown peaks were similar with 3 diester diterpene alkaloids. The established method is accurate, reliable and repeatable, and can provide reference for revealing change rule of index components and illuminating processing principle in the process of Heishunpian.

[Discrimination of Coptidis Rhizoma and its processed products by odor objectify].

Different processed products of Coptidis Rhizoma have its unique odor, which is an important assessment index for pro- cessed products identification of Coptidis Rhizoma. Objectify odor as an entry point in this study, an electronic nose technology was used, and a suitable method for Coptidis Rhizoma measurement was built firstly. Then different processed products of Coptidis Rhizoma were detected by the method built. Finally, different processed products were identified by combining with chemometrics based on the objective odor information obtained. Electronic nose detection indicated that a significant difference in odor between different processed products was performed. Coptidis Rhizoma processed or not can be distinguished based on statistical quality control (SQC) and soft independent modeling of class analogy (SIMCA). Principle component analysis (PCA) model showed that Coptidis Rhizoma and its various processed products discriminated obviously. In addition, in order to identify the processed products of Coptidis Rhizoma, a correct recognition rate of 100% was acquired by discriminant factor analysis (DFA) , and the initial identification rate and cross-validation recognition rate of linear discriminant analysis (LDA) is 100%, 94.4% respectively. In conclusion, differentiationin odor of different processed Coptidis Rhizoma was performed by the electronic nose technology used, and different products Coptidis Rhizoma were dis- criminated by combining with chemometrics. This research can be a reference for objective identification in odor of traditional Chinese medicine, and is good for the inheritance and development of traditional experience in odor identification.

Enzyme-etching technique to fabricate micropatterns of aligned collagen fibrils.

A technique to tailor-make pre-coated, pre-aligned bovine collagen fibrils, derived from neonatal cardiomyocytes, on the surface of a glass slide into a designated pattern is reported. The unwanted collagen-coated area was erased by a collagenase solution and the tailored area was retained by attaching a microfabricated polydimethylsiloxane stamp directly to the collagen-coated surface. Using this technique, collagen patterns with designated orientations and with clear pattern boundaries and defined shapes were fabricated.

[Theory and research of dryness in traditional Chinese medicine].

Dryness is the inherent performance in traditional Chinese medicine. Dryness with a specific efficacy and side effect can be reduced suitably by processing and compatibility in the clinical application. Nowadays domestic scholars have developed research of dryness in traditional Chinese medicine. However, it remains problems such as evaluation index of dryness not clear. This paper takes medical literature mining technology to analyze the historical origin and features of dryness theory. Combing the modern literatures to explicate the dryness' research status and existing problems. Putting forward the traditional Chinese medicine and research should adopt multidisciplinary knowledge and study the system of comprehensive evaluation. Dryness is expected to further application in traditional Chinese medicine clinical research.

A comprehensive investigation on the receptor BSG expression reveals the potential risk of healthy individuals and cancer patients to 2019-nCoV infection.

BACKGROUND: Coronavirus disease-2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a newly emerging coronavirus. BSG (basigin) is involved in the tumorigenesis of multiple tumors and recently emerged as a novel viral entry receptor for SARS-CoV-2. However, its expression profile in normal individuals and cancer patients are still unclear. METHODS: We performed a comprehensive analysis of the expression and distribution of BSG in normal tissues, tumor tissues, and cell lines via bioinformatics analysis and experimental verification. In addition, we investigated the expression of BSG and its isoforms in multiple malignancies and adjacent normal tissues, and explored the prognostic values across pan-cancers. Finally, we conducted function analysis for co-expressed genes with BSG. RESULTS: We found BSG was highly conserved in different species, and was ubiquitously expressed in almost all normal tissues and significantly increased in some types of cancer tissues. Moreover, BSG at mRNA expression level was higher than ACE2 in normal lung tissues, and lung cancer tissues. High expression of BSG indicated shorter overall survival (OS) in multiple tumors. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that BSG is mostly enriched in genes for mitochondria electron transport, oxidoreduction-driven active transmembrane transporter activity, mitochondrial inner membrane, oxidative phosphorylation, and genes involving COVID-19. CONCLUSIONS: Our present work emphasized the value of targeting BSG in the treatment of COVID-19 and cancer, and also provided several novel insights for understanding the SARS-CoV-2 pandemic.

Electroacupuncture Promotes Nerve Regeneration and Functional Recovery Through Regulating lncRNA GAS5 Targeting miR-21 After Sciatic Nerve Injury.

Although the benefits of electroacupuncture (EA) for peripheral nerve injury (PNI) are well accepted in clinical practice, the underlying mechanism remains incompletely elucidated. In our study, we observed that EA intervention led to a reduction in the expression of the long non-coding RNA growth-arrest-specific transcript 5 (GAS5) and an increased in miR-21 levels within the injured nerve, effectively promoting functional recovery and nerve regeneration following sciatic nerve injury (SNI). In contrast, administration of adeno-associated virus expressing GAS5 (AAV-GAS5) weakened the therapeutic effect of EA. On the other hand, both silencing GAS5 and introducing a miR-21 mimic prominently enhanced the proliferation activity and migration ability of Schwann cells (SCs), while also inhibiting SCs apoptosis. On the contrary, inhibition of SCs apoptosis was found to be mediated by miR-21. Additionally, overexpression of GAS5 counteracted the effects of the miR-21 mimic on SCs. Moreover, SCs that transfected with the miR-21 mimic promoted neurite growth in hypoxia/reoxygenation-induced neurons, which might be prevented by overexpressing GAS5. Furthermore, GAS5 was found to be widely distributed in the cytoplasm and was negatively regulated by miR-21. Consequently, the targeting of GAS5 by miR-21 represents a potential mechanism through which EA enhances reinnervation and functional restoration following SNI. Mechanistically, the GAS5/miR-21 axis can modulate the proliferation, migration, and apoptosis of SCs while potentially influencing the neurite growth of neurons.