Targeting LRP6: A new strategy for cancer therapy.

Targeting specific molecular drivers of tumor growth is a key approach in cancer therapy. Among these targets, the low-density lipoprotein receptor-related protein 6 (LRP6), a vital component of the Wnt signaling pathway, has emerged as an intriguing candidate. As a cell-surface receptor and vital co-receptor, LRP6 is frequently overexpressed in various cancer types, implicating its pivotal role in driving tumor progression. The pursuit of LRP6 as a target for cancer treatment has gained substantial traction, offering a promising avenue for therapeutic intervention. Here, this comprehensive review explores recent breakthroughs in our understanding of LRP6's functions and underlying molecular mechanisms, providing a profound discussion of its involvement in cancer pathogenesis and drug resistance. Importantly, we go beyond discussing LRP6's role in cancer by discussing diverse potential therapeutic approaches targeting this enigmatic protein. These approaches encompass a wide spectrum, including pharmacological agents, natural compounds, non-coding RNAs, epigenetic factors, proteins, and peptides that modulate LRP6 expression or disrupt its interactions. In addition, also discussed the challenges associated with developing LRP6 inhibitors and their advantages over Wnt inhibitors, as well as the drugs that have entered phase II clinical trials. By shedding light on these innovative strategies, we aim to underscore LRP6's significance as a valuable and multifaceted target for cancer treatment, igniting enthusiasm for further research and facilitating translation into clinical applications.

Short-Chain Acyl-CoA Dehydrogenase as a Therapeutic Target for Cardiac Fibrosis.

ABSTRACT: Cardiac fibrosis is considered as unbalanced extracellular matrix production and degradation, contributing to heart failure. Short-chain acyl-CoA dehydrogenase (SCAD) negatively regulates pathological cardiac hypertrophy. The purpose of this study was to investigate the possible role of SCAD in cardiac fibrosis. In vivo experiments were performed on spontaneously hypertensive rats (SHR) and SCAD-knockout mice. The cardiac tissues of hypertensive patients with cardiac fibrosis were used for the measurement of SCAD expression. In vitro experiments, with angiotensin II (Ang II), SCAD siRNA and adenovirus-SCAD were performed using cardiac fibroblasts (CFs). SCAD expression was significantly decreased in the left ventricles of SHR. Notably, swim training ameliorated cardiac fibrosis in SHR in association with the elevation of SCAD. The decrease in SCAD protein and mRNA expression levels in SHR CFs were in accordance with those in the left ventricular myocardium of SHR. In addition, SCAD expression was downregulated in CFs treated with Ang II in vitro, and SCAD siRNA interference induced the same changes in cardiac fibrosis as Ang II-treated CFs, while adenovirus-SCAD treatment significantly reduced the Ang II-induced CFs proliferation, alpha smooth muscle actin (α-SMA), and collagen expression. In SHR infected with adenovirus-SCAD, the cardiac fibrosis of the left ventricle was significantly decreased. However, cardiac fibrosis occurred in conventional SCAD-knockout mice. SCAD immunofluorescence intensity of cardiac tissue in hypertensive patients with cardiac fibrosis was lower than that of healthy subjects. Altogether, the current experimental outcomes indicate that SCAD has a negative regulatory effect on cardiac fibrosis and support its potential therapeutic target for suppressing cardiac fibrosis.

Ras inhibitor farnesylthiosalicylic acid conjugated with IR783 dye exhibits improved tumor-targeting and altered anti-breast cancer mechanisms in mice.

Ras has long been viewed as a promising target for cancer therapy. Farnesylthiosalicylic acid (FTS), as the only Ras inhibitor has ever entered phase II clinical trials, has yielded disappointing results due to its strong hydrophobicity, poor tumor-targeting capacity, and low therapeutic efficiency. Thus, enhancing hydrophilicity and tumor-targeting capacity of FTS for improving its therapeutic efficacy is of great significance. In this study we conjugated FTS with a cancer-targeting small molecule dye IR783 and characterized the anticancer properties of the conjugate FTS-IR783. We showed that IR783 conjugation greatly improved the hydrophilicity, tumor-targeting and therapeutic potential of FTS. After a single oral administration in Balb/c mice, the relative bioavailability of FTS-IR783 was increased by 90.7% compared with FTS. We demonstrated that organic anion transporting polypeptide (OATP) and endocytosis synergistically drove the uptake of the FTS-IR783 conjugate in breast cancer MDA-MB-231 cells, resulting in superior tumor-targeting ability of the conjugate both in vitro and in vivo. We further revealed that FTS-IR783 conjugate could bind with and directly activate AMPK rather than affecting Ras, and subsequently regulate the TSC2/mTOR signaling pathway, thus achieving 2-10-fold increased anti-cancer therapeutic efficacy against 6 human breast cancer cell lines compared to FTS both in vivo and in vitro. Overall, our data highlights a promising approach for the modification of the anti-tumor drug FTS using IR783 and makes it possible to return FTS back to the clinic with a better efficacy.

Downregulation of miR-96-5p Inhibits mTOR/NF-κb Signaling Pathway via DEPTOR in Allergic Rhinitis.

BACKGROUND: This study aims to investigate the regulatory effect of microRNA-96-5p (miR-96-5p) in the pathophysiological process of allergic rhinitis (AR). METHODS: Nasal mucosal tissue samples were collected from AR patients and healthy controls. An in vitro AR model was established by stimulating human nasal epithelial cells (HNECs) with interleukin (IL)-13. The expressions of target genes and proteins were measured by qPCR, Western blot, or ELISA. Dual-luciferase reporter assay and pull-down assay were performed to confirm the interaction between miR-96-5p and DEP domain-containing mammalian target of rapamycin-interacting protein (DEPTOR). RESULTS: The level of miR-96-5p was increased while the expression of DEPTOR was decreased in AR patients. The expressions of proinflammatory cytokines were markedly increased and the mammalian target of rapamycin (mTOR)/NF-κB pathway was activated in HNECs following IL-13 stimulation. miR-96-5p downregulation alleviated the stimulated function by IL-13. DEPTOR was the target of miR-96-5p. Knockdown of DEPTOR reversed the function of miR-96-5p inhibitor on IL-13-stimulated HNECs. CONCLUSIONS: The current study showed that miR-96-5p and DEPTOR were aberrantly expressed in AR nasal mucosa. miR-96-5p knockdown inhibited the production of inflammatory cytokines and the activation of mTOR/NF-κB pathway via targeting DEPTOR. These findings suggested that miR-96-5p might be used as a diagnostic marker and therapeutic target for the treatment of AR.

The novel FAT4 activator jujuboside A suppresses NSCLC tumorigenesis by activating HIPPO signaling and inhibiting YAP nuclear translocation.

FAT atypical cadherin 4 (FAT4) has been identified as a tumor suppressor in lung cancers. However, no agent for lung cancer treatment targeting FAT4 has been used in the clinic. Jujuboside A (JUA) is a major active compound in Semen Ziziphi Spinosae. Semen Ziziphi Spinosae is a traditional Chinese herbal medicine used clinically for tumor treatment to improve patients' quality of life. However, the anti-lung cancer activity and the underlying mechanisms of JUA are not yet fully understood. Here, we demonstrated the anti-lung cancer activity of JUA in two lung cancer mice models and three non-small cell lung cancer (NSCLC) cell lines, and further illustrated its underlying mechanisms. JUA suppressed the occurrence and development of lung cancer and extended mice survival in vivo, and suppressed NSCLC cell activities through cell cycle arrest, proliferation suppression, stemness inhibition and senescence promotion. Moreover, JUA directly bound with and activated FAT4, subsequently activating FAT4-HIPPO signaling and inhibiting YAP nuclear translocation. Knockdown of FAT4 diminished JUA's effects on HIPPO signaling, YAP nuclear translocation, cell proliferation and cellular senescence. In conclusion, JUA significantly suppressed NSCLC tumorigenesis by regulating FAT4-HIPPO-YAP signaling. Our findings suggest that JUA is a novel FAT4 activator that can be developed as a promising NSCLC therapeutic agent targeting the FAT4-HIPPO-YAP pathway.

Effects of short-chain acyl-CoA dehydrogenase on cardiomyocyte apoptosis.

Short-chain acyl-CoA dehydrogenase (SCAD), a key enzyme of fatty acid ß-oxidation, plays an important role in cardiac hypertrophy. However, its effect on the cardiomyocyte apoptosis remains unknown. We aimed to determine the role of SCAD in tert-butyl hydroperoxide (tBHP)-induced cardiomyocyte apoptosis. The mRNA and protein expression of SCAD were significantly down-regulated in the cardiomyocyte apoptosis model. Inhibition of SCAD with siRNA-1186 significantly decreased SCAD expression, enzyme activity and ATP content, but obviously increased the content of free fatty acids. Meanwhile, SCAD siRNA treatment triggered the same apoptosis as cardiomyocytes treated with tBHP, such as the increase in cell apoptotic rate, the activation of caspase3 and the decrease in the Bcl-2/Bax ratio, which showed that SCAD may play an important role in primary cardiomyocyte apoptosis. The changes of phosphonate AMP-activated protein kinase α (p-AMPKα) and Peroxisome proliferator-activated receptor α (PPARα) in cardiomyocyte apoptosis were consistent with that of SCAD. Furthermore, PPARα activator fenofibrate and AMPKα activator AICAR treatment significantly increased the expression of SCAD and inhibited cardiomyocyte apoptosis. In conclusion, for the first time our findings directly demonstrated that SCAD may be as a new target to prevent cardiomyocyte apoptosis through the AMPK/PPARα/SCAD signal pathways.

Epigenetic regulation of active Chinese herbal components for cancer prevention and treatment: A follow-up review.

Epigenetic modifications include DNA methylation, histone modification, and other patterns. These processes are associated with carcinogenesis and cancer progression. Thus, epigenetic modification-related enzymes, such as DNA methyltransferases (DNMTs), histone methyltransferases (HMTs), histone demethylases (HDMTs), histone acetyltransferases (HATs), and histone deacetylases (HDACs), as well as some related proteins, including methyl-CpG binding proteins (MBPs) and DNMT1-associated protein (DMAP 1), are considered as potential targets for cancer prevention and therapy. Numerous natural compounds, mainly derived from Chinese herbs and chemically ranging from polyphenols and flavonoids to mineral salts, inhibit the growth and development of various cancers by targeting multiple genetic and epigenetic alterations. This review summarizes the epigenetic mechanisms by which active compounds from Chinese herbs exert their anti-cancer effect. A subset of these compounds, such as curcumin and resveratrol, affect multiple epigenetic processes, including DNMT inhibition, HDAC inactivation, MBP suppression, HAT activation, and microRNA modulation. Other compounds also regulate epigenetic modification processes, but the underlying mechanisms and clear targets remain unknown. Accordingly, further studies are required.

Changes in short-chain acyl-coA dehydrogenase during rat cardiac development and stress.

This study was designed to investigate the expression of short-chain acyl-CoA dehydrogenase (SCAD), a key enzyme of fatty acid ß-oxidation, during rat heart development and the difference of SCAD between pathological and physiological cardiac hypertrophy. The expression of SCAD was lowest in the foetal and neonatal heart, which had time-dependent increase during normal heart development. In contrast, a significant decrease in SCAD expression was observed in different ages of spontaneously hypertensive rats (SHR). On the other hand, swim-trained rats developed physiological cardiac hypertrophy, whereas SHR developed pathological cardiac hypertrophy. The two kinds of cardiac hypertrophy exhibited divergent SCAD changes in myocardial fatty acids utilization. In addition, the expression of SCAD was significantly decreased in pathological cardiomyocyte hypertrophy, however, increased in physiological cardiomyocyte hypertrophy. SCAD siRNA treatment triggered the pathological cardiomyocyte hypertrophy, which showed that the down-regulation of SCAD expression may play an important role in pathological cardiac hypertrophy. The changes in peroxisome proliferator-activated receptor α (PPARα) was accordant with that of SCAD. Moreover, the specific PPARα ligand fenofibrate treatment increased the expression of SCAD and inhibited pathological cardiac hypertrophy. Therefore, we speculate that the down-regulated expression of SCAD in pathological cardiac hypertrophy may be responsible for 'the recapitulation of foetal energy metabolism'. The deactivation of PPARα may result in the decrease in SCAD expression in pathological cardiac hypertrophy. Changes in SCAD are different in pathological and physiological cardiac hypertrophy, which may be used as the molecular markers of pathological and physiological cardiac hypertrophy.

Integrated biosensor array for multiplex biomarkers cancer diagnosis via in-situ self-assembly carbon nanotubes with an ordered inverse-opal structure.

To enhance the precision and reliability of early disease detection, especially in malignancies, an exhaustive investigation of multi-target biomarkers is essential. In this study, an advanced integrated electrochemical biosensor array that demonstrates exceptional performance was constructed. This biosensor was developed through a controllable porous-size mechanism and in-situ modification of carbon nanotubes (CNTs) to quantify multiplex biomarkers-specifically, C-reaction protein (CRP), carbohydrate antigen 125 (CA125), and carcinoembryonic antigen (CEA)-in human serum plasma. The fabrication process involved creating a highly ordered three-dimensional inverse-opal structure with the CNTs (pCNTs) modifier through microdroplet-based microfluidics, confined spatial self-assembly of nanoparticles, and chemical wet-etching. This innovative approach allowed for direct in-situ modification of nanomaterial onto the surface of electrode array, eliminating secondary transfer and providing exceptional control over structure and stability. The outstanding electrochemical performance was achieved through the synergistic effect of the pCNTs nanomaterial, aptamer, and horseradish peroxidase-labeled (HRP-) antibody. Additionally, the integrated biosensor array platform comprised multiple individually addressable electrode units (n = 11), enabling simultaneous multi-parallel/target testing, thereby ensuring accuracy and high throughput. Crucially, this integrated biosensor array accurately quantified multiplex biomarkers in human serum, yielding results comparable to commercial methods. This integrated technology holds promise for point-of-care testing (POCT) in early disease diagnosis and biological analysis.

Multiplex signal amplification for ultrasensitive CRP assay via integrated electrochemical biosensor array using MOF-derived carbon material and aptamers.

Accurate and precise detection of disease-associated proteins, such as C-reactive protein (CRP), remains a challenge in biosensor development. Herein, we present a novel approach－an integrated disposable aptasensor array－designed for precise, ultra-sensitive, and parallel detection of CRP in plasma samples. This integrated biosensing array platform enables multiplex parallel testing, ensuring the accuracy and reliability in sample analysis. The ultra-sensitivity of this biosensor is achieved through multiplex signal amplification. Leveraging the superior conductivity and extensive surface area of MOF-derived nanoporous carbon material (CMOF), the biosensor enhances recognition elements (aptamers) by catalyzing the horseradish peroxidase (HRP) label enzyme reaction to multiply the number of probe molecules. Optimized conditions yielded exceptional performance, exhibiting high accuracy (relative standard deviation, RSD≤10.0 %), a low detection limit (0.3 pg/mL, S/N = 3), ultra-sensitivity (0.16 µA/ng mL-1 mm-2), and a rapid response (seven parallel tests within 60 min). Importantly, this multi-unit integrated disposable aptasensor array accurately quantified CRP in human serum, demonstrating comparable results to commercial enzyme-linked immunosorbent assay (ELISA). This technology showcases promise for detecting various biomarkers using a unified approach, presenting an appealing strategy for early disease diagnosis and biological analysis.

Fufang Luohanguo Qingfei granules reduces influenza virus susceptibility via MAVS-dependent type I interferon antiviral signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Luohanguo Qingfei granules (LQG) is a Chinese patent medicine, clinically used to treat flu-like symptoms including cough with yellow phlegm, impeded phlegm, dry throat and tongue. However, the protective activity of LQG against influenza infection is indeterminate. AIM OF THE STUDY: This study is to investigate the therapeutic effect of LQG on influenza infection and elucidate its underlying mechanism. MATERIALS AND METHODS: In vivo: A viral susceptible mouse model induced by restraint stress was established to investigate LQG's beneficial effects on influenza susceptibility. MAVS knockout (Mavs-/-) mice were used to verify the potential mechanism of LQG. In vitro: Corticosteroid (CORT)-treated A549 cells were employed to identify the active ingredients in LQG. Mice morbidity and mortality were monitored daily for 21 days. Histopathologic changes and inflammatory cytokines in lung tissues were examined by H&E staining and ELISA. RNA-seq was used to explore the signaling pathway influenced by LQG and further confirmed by qPCR. Immunoblotting and immunohistochemistry (IHC) were used to determine the protein levels. CO-IP and DARTS were applied to detect protein-protein interaction and compound-protein interaction, respectively. RESULTS: LQG effectively attenuated the susceptibility of restrained mice to H1N1 infection. LQG significantly boosted the production of IFN-ß transduced by mitochondrial antiviral-signaling protein (MAVS), while MAVS deficiency abrogated its protective effects on restrained mice infected with H1N1. Moreover, in vitro studies further revealed that mogroside Ⅱ B, amygdalin, and luteolin are potentially active components of LQG. CONCLUSION: These results suggested that LQG inhibited the mitofusin 2 (Mfn2)-mediated ubiquitination of MAVS by impeding the E3 ligase synoviolin 1 (SYVN1) recruitment, thereby enhancing IFN-ß antiviral response. Overall, our work elaborates a potential regimen for influenza treatment through reduction of stress-induced susceptibility.

Intentional replantation and dental autotransplantation of mandibular posterior teeth: Two case reports.

BACKGROUND: Intentional replantation and dental autotransplantation are 2 similar techniques both involving atraumatic tooth extraction, visualization of the root, and replantation. They are considered as the last resort for unsalvageable teeth. The author aims to describe 2 mandibular posterior teeth with serious periapical lesions which are resolved by intentional replantation and dental autotransplantation, respectively. CASE SUMMARY: In case 1, a 45-year-old male patient received root canal treatment because of a cracked mandible right first molar with periapical lesions. An endodontic file was separated in the apical third of the mesiolingual root canal. After conventional canal filling of the other root canals, the molar was atraumatically extracted. The separated instrument was removed, the mesiolingual root received a retrograde filling and the molar was replanted. At the 3-month follow up, the patient was asymptomatic and the X-ray picture showed no detectable root resorption and ankylosis. In case 2, a 29-year-old woman reported discomfort during occlusal loading after a root canal treatment and a coronal restoration of the mandibular right first molar. Radiographs showed a low-density shadow in the mesial apical and in the root furcation area of the mandibular first molar so the patient was diagnosed as chronic periapical periodontitis. After the removal of the affected tooth, the extraction socket was thoroughly debrided and irrigated. The intact mandibular right third molar with similar dimensions was extracted by minimally invasive procedure and transplanted. The donor tooth was fixed by a fiber-splint for 1 month and a root canal treatment was performed 2 weeks after surgery. After 1 year, clinical and radiographical examination revealed functional and periodontal healing. CONCLUSIONS: These 2 reports present the successful management of intentional replantation and dental autotransplantation. Both procedures are recommended after nonsurgical endodontic treatment, especially when apical microsurgery is not an option, for example because of difficult accessibility or patient preference.

Scutellaria baicalensis: a promising natural source of antiviral compounds for the treatment of viral diseases.

Viruses, the smallest microorganisms, continue to present an escalating threat to human health, being the leading cause of mortality worldwide. Over the decades, although significant progress has been made in the development of therapies and vaccines against viral diseases, the need for effective antiviral interventions remains urgent. This urgency stems from the lack of effective vaccines, the severe side effects associated with current drugs, and the emergence of drug-resistant viral strains. Natural plants, particularly traditionally-used herbs, are often considered an excellent source of medicinal drugs with potent antiviral efficacy, as well as a substantial safety profile. Scutellaria baicalensis, a traditional Chinese medicine, has garnered considerable attention due to its extensive investigation across diverse therapeutic areas and its demonstrated efficacy in both preclinical and clinical trials. In this review, we mainly focused on the potential antiviral activities of ingredients in Scutellaria baicalensis, shedding light on their underlying mechanisms of action and therapeutic applications in the treatment of viral infections.

Total flavonoids of Litchi seed attenuate stem cell-like properties in breast cancer by regulating Notch3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Breast cancer has been the most commonly-diagnosed cancer worldwide, and the treatment and prognosis of which are often limited by breast cancer stem cells (BCSCs). Litchi seeds have shown good anti-cancer activity in various cancers including prostate cancer, lung cancer and breast cancer. However, the activity and underlying mechanism of Litchi seeds against BCSCs remain unknown. AIM OF THE STUDY: To investigate the activity and mechanism of total flavonoids of litchi seed (TFLS) against BCSCs in vitro and in vivo. MATERIALS AND METHODS: Two orthotopic xenograft mouse models were established using HCC1806 cells pretreated or untreated with TFLS to determine whether TFLS could target BCSCs in vivo. Mammosphere formation and flow cytometry assays were employed to evaluate the effect of TFLS on BCSCs in vitro. The underlying mechanism was investigated using RT-qPCR, Western blot, immunohistochemistry and immunofluorescence experiments. RESULTS: TFLS could significantly inhibit the viability of HCC1806, MCF-7 and HCC1937 cells in vitro and suppress the growth of HCC1806 cells in vivo. TFLS attenuated stem cell-like properties of breast cancer through reducing the percentage of CD44+CD24-/low cells, inhibiting the mammospheres formation and down-regulating the mRNA and protein levels of cancer stem cells related markers (Oct4, Nanog, Sox2) in MCF-7 and HCC1806 cells. Meanwhile, TFLS suppressed the tumor-initiating ability of BCSCs via reducing the percentage of CD44+CD24-/low cells in tumor and lowering tumor incidence rate in orthotopic xenograft mice. In addition, TFLS treatments restricted the expression and nuclear translocation of Notch3, subsequently down-regulated Hes1 and Runx2 expressions. CONCLUSIONS: TFLS could suppress the growth of breast cancer and eliminate breast cancer stem cells by inhibiting the Notch3 signaling pathway.

Sensitive electrochemical assay of acetaminophen based on 3D-hierarchical mesoporous carbon nanosheets.

Acetaminophen plays a key role in first-line Covid-19 cure as a supportive therapy of fever and pain. However, overdose of acetaminophen may give rise to severe adverse events such as acute liver failure in individual. In this work, 3D-hierarchical mesoporous carbon nanosheet (hMCNS) microspheres with superior properties were fabricated using simple and quick strategy and applied for sensitive quantification of acetaminophen in pharmaceutical formulation and rat plasmas after administration. The hMCNS microspheres are prepared via chemical etching of zinc oxide (ZnO) nanoparticles from a zinc-gallic acid precursor composite (Zn-GA) synthesized by high-temperature anaerobic pyrolysis. The obtained hMCNS could enhance analytes accessibility and accelerate proton transfer in the interface, hence increasing the electrochemical performance. Under optimized experimental conditions, the proposed electrochemical sensor achieves a detection limit of 3.5 nM for acetaminophen. The prepared electrochemical sensor has been successfully applied for quantification of acetaminophen in pharmaceutical formulations and the rat plasma samples before and after administration. Meanwhile, this sensor is compared with high-performance liquid chromatography (HPLC) as a reference technology, showing an excellent accuracy. Such an electrochemical sensor has great potential and economic benefits for applications in the fields of pharmaceutical assay and therapeutic drug monitoring (TDM).

Peripheral Circulating Exosomal-miRNAs Potentially Mediate the Sensitivity to Interferon Treatment in Chronic Hepatitis B Virus Patients.

Pegylated interferon alfa-2b (Peg-IFN α-2b), a first-line treatment for hepatitis B virus (HBV) infection, can significantly achieve HBsAg clearance in clinic. However, only 30-40% of patients had achieved HBsAg clearance after Peg-IFN α-2b administration. The biological targets and the underline mechanisms that distinguish sensitive and insensitive populations to interferon therapy are still unclear. In the present study, only 33.33% of patients achieved HBsAg loss after 48 weeks of Peg-IFN α-2b therapy. Thirty-six exosomal-microRNAs (miRNAs) in the sensitive group were identified that might induce sensitivity specifically, whereas 32 exosomal-miRNAs in the insensitive group were identified that might induce insensitive specifically. Among these miRNAs, five miRNAs (miR-425-5p, miR-8485, miR-619-5p, miR-181a-5p, and miR-484) might increase the sensitivity to Peg-IFN α-2b therapy by regulating key genes GSK3B, KRAS, FLT1, or GRB2, whereas, 13 miRNAs (miR-195-5p, miR-215-5p, miR-9-5p, miR-130a-3p, miR-214-3p, miR-149-5p, miR-429, miR-200b-3p, miR-200c-3p, miR-16-2-3p, miR-141-3p, miR-200a-3p, and miR-218-5p) might decrease the sensitivity to Peg-IFN α-2b therapy by regulating key genes, FGF2, GSK3B, PDGFRA, FGFR1, KRAS, FLT1, MYC, TGFB2, EFNA1, MAPK9, or GRB2. Furthermore, seven novel miRNAs, namely Novel_352, Novel_459, Novel_527, Novel_677, Novel_717, Novel_749, and Novel_801 were found to be downregulated specifically in the sensitive group, whereas, Novel_142 and Novel_664 were found to be downregulated specifically in the insensitive group. Our data indicate that the serum exosomal-miRNAs could be involved in regulating the sensitivity of chronic HBV (CHB) patients to Peg-IFN α-2b therapy, which might suggest potential novel therapeutic biomarkers and standard options for CHB patients. Clinical Trials.gov ID: NCT04035837.

Effects of Gypenoside XLIX on fatty liver cell gene expression in vitro: a genome-wide analysis.

OBJECTIVE: To perform Genome-wide analysis of Gypenoside XLIX (Gyp-XLIX) in the treatment of fatty liver cells. METHODS: The gene profiles of 3 normal liver cells, 3 fatty liver cells, and 3 fatty liver cells treated with Gyp-XLIX were detected by high-throughput sequencing to identify the differentially expressed genes (DEGs) in fatty liver treated by Gyp-XLIX. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to explore the biological functions of DEGs. By constructing lncRNA-mRNA co-expression network of DEGs, network node genes were mined. Possible target genes of differentially expressed lncRNA were predicted by cis regulation. RESULTS: 782 DEGs were screened out; that is, 172 genes were highly expressed in fatty liver cells, and the expression decreased to the level of normal liver cells after Gyp-XLIX treatment; 610 genes were under expressed in fatty liver cells, and the expression increased to the level of normal liver cells after Gyp-XLIX treatment. Functional analysis of KEGG and GO showed that DEGs process DNA-binding transcription factor activity and ion transmembrane transporter activity in the plasma membrane region. This mediates glycerophospholipid metabolism, bile secretion, fatty acid degradation and other signaling pathways. lncRNA analysis showed that the expression of 16 lncRNAs was low in fatty liver cells, and the expression was increased to the level of normal liver cells after Gyp-XLIX treatment. Target gene prediction showed that 16 differentially expressed lncRNAs had cis potential to regulate target genes, among which lncRNA RPARP-AS1 had a high degree of relationship with other genes. lncRNA-mRNA co-expression network results showed that lncRNA RPARP-AS1 may acted on NFKB2. CONCLUSION: LncRNA was differentially expressed in fatty liver cells and Gyp-XLIX treated fatty liver cells, and lncRNA RPARP-AS1 may be a regulatory gene in Gyp-XLIX treated fatty liver.

Effect of Hanna Somatic Education on Low Back and Neck Pain Levels.

Background: Neck and low back pain are very common worldwide. Hanna somatic education (HSE) is a method of neuromuscular (mind-body) movement retraining that helps in managing pain, but its efficacy has not yet been studied. Objective: To evaluate the clinical effect of HSE on low back and neck pain and determine differences in pain, use of pain medication, and number of doctor visits before and after 6 months of HSE sessions. Methodology: This retrospective study included patients with neck and/or low back pain of >2-month duration who underwent HSE sessions between January 2016 and January 2018 and completed a minimum one follow-up session. Two to five one-to-one sessions of 40-60 min once every 1-2 weeks for 2-8 weeks were provided for each patient. Pain levels were recorded at each visit using the Wong-Baker FACES Pain Rating Scale. Data regarding medication use and number of doctor visits for pain management were also recorded. Results: A total of 103 patients were included, of which 81 (78.6%) were female. Completing a mean 2.8 HSE sessions resulted in a significant pain level reduction. There were significant reductions in the mean low back, neck, and low back + neck pain values between the first and the last visits (P < 0.001). In the 6 months before and after the HSE intervention, the number of patients using pain medication decreased from 53 (53.5%) to 14 (13.6%), respectively, and the mean number of doctor visits reduced significantly from 2 (±1.6) to 0.5 (±1.16) (P < 0.001), respectively. Conclusion: Clinical sessions of HSE were found to significantly reduce chronic spinal pain. Further investigations are recommended regarding evidence-based treatment of HSE in patients with muscles pain.

Triple signal-enhancing electrochemical aptasensor based on rhomboid dodecahedra carbonized-ZIF67 for ultrasensitive CRP detection.

C-reactive protein (CRP) is one of the most sensitive acute-phase reactants, which is an early stage indicator of cardiovascular disease and infectious inflammation in clinic. However, it is still challenging to accurately quantification the trace content of CRP molecules in plasma samples. In this work, we propose an ultrasensitive electrochemical CRP aptasensor based on rhomboid dodecahedra carbonized-ZIF67 loaded with gold nanoparticle modified by aptamer. Aptamer biomolecules are binded to AuNPs via Au-thiol bonds for selectively capturing CRPs. The ultrasensitivity is achieved based on triple signal enhancing strategy: enhancing the specific surface area via the rhomboid dodecahedra structure of ZIF67, increasing the conductivity via carbonization of ZIF67, and multiplying the number of probe molecules via an enzyme catalyzed reaction. Experimental parameters, including the volume of C-ZIF67 dispersion, electrodeposition time of AuNPs, incubation time of aptamer-CRP and aptamer-CRP concentration, are systemically investigated and optimized. Under optimal conditions, the proposed biosensor shows excellent sensing performance with the limit of detection (LOD) of 0.44 pg mL-1 (S/N = 3), and a broad linear dynamic range of 10 pg mL-1 ‒ 10 µg mL-1 within the total readout time of 5 min. This work provides an effective electrochemical biosensor for CRP assay in plasma, being highly potential for applications in bioanalysis and point-of-care (POC) clinical diagnosis.

Application value of computed tomography and magnetic resonance imaging three-dimensional reconstruction and digital subtraction angiography in percutaneous transhepatic cholangial drainage.

Objective: This study aims to explore the application value of computed tomography (CT) three-dimensional (3D) reconstruction, magnetic resonance imaging (MRI) 3D reconstruction, and conventional digital subtraction angiography (DSA) fluoroscopy in percutaneous transhepatic cholangial drainage (PTCD). Methods: The clinical data of 180 patients with obstructive jaundice requiring PTCD from December 2017 to December 2021 were retrospectively analyzed. Following PTCD, CT 3D reconstruction, MRI 3D reconstruction, and conventional DSA fluoroscopy were conducted, after which the surgical success rates, liver function results, and postsurgical complications were compared. Results: The puncture accuracies under CT 3D reconstruction, MRI 3D reconstruction, and conventional DSA fluoroscopy were 90.0% (54/60), 96.7% (58/60), and 80% (48/60), respectively. The degree of jaundice and epigastric discomfort was relieved in all three groups after surgery, while a significant reduction in the levels of total bilirubin and direct bilirubin was observed relative to the levels before surgery (P < 0.05). The incidences of complications in the CT 3D reconstruction, MRI 3D reconstruction, and conventional DSA fluoroscopy groups were 6.7% (4/60), 3.3% (2/60), and 13.3% (8/60), respectively, and the differences among the three groups were statistically significant (P < 0.05). Conclusion: Conducting conventional enhanced CT and MRI scans in patients before surgery might be more practical than the conventional puncture method. Among the methods under study, MRI 3D reconstruction was found to be safer and more feasible than CT 3D reconstruction and conventional DSA fluoroscopy in PTCD. MRI 3D reconstruction could reduce the degree of jaundice, improve the success rate of surgery, reduce the incidence of complications due to surgery, and improve the patients' tolerance to surgery.