Predominant determinants for evaluation of right parasternal approach in transthoracic echocardiography in aortic stenosis: a study based on three-dimensional cardiac computed tomography analysis.

The maximum blood flow velocity through the aortic valve (AVmax) using Doppler transthoracic echocardiography (TTE) is important in assessing the severity of aortic stenosis (AS). The right parasternal (RP) approach has been reported to be more useful than the apical approach, but the anatomical rationale has not been studied. We aimed to clarify the influence of the angle formed by the ascending aorta and left ventricle on Doppler analysis by TTE (Sep-Ao angle) and three-dimensional multidetector computed tomography (3D-MDCT) in patients with AS. A total of 151 patients evaluated using the RP approach and 3D-MDCT were included in this study. The Sep-Ao angle determined using TTE was compared with that determined using 3D-MDCT analysis. In MDCT analysis, the left ventricular (LV) axis was measured in two ways and the calcification score was calculated simultaneously. The Sep-Ao angle on TTE was consistent with that measured using 3D-MDCT. In patients with an acute Sep-Ao angle, the Doppler angle in the apical approach was larger, potentially underestimating AVmax. Multivariate analysis revealed that an acute Sep-Ao angle, large Doppler angle in the apical approach, smaller Doppler angle in the RP approach, and low aortic valve calcification were independently associated with a higher AVmax in the RP approach than in the apical approach. The Sep-Ao angle measured using TTE reflected the 3D anatomical angle. In addition to measurements using the RP approach, technical adjustments to minimize the Doppler angle to avoid bulky calcification should always be noted for accurate assessment.

Suppressive Activity of Boiogito, a Japanese Traditional Kampo Medicine, on Periostin Secretion in Human Fibroblast-Like Synoviocytes In Vitro.

Background Knee osteoarthritis (KOA) is a prevalent degenerative disease that affects the knee joints, particularly among individuals aged over 40 years. It leads to pain, stiffness, and reduced quality of life; affects approximately 300 million individuals worldwide; and is increasing, particularly in developed nations. Although treatments for KOA range from conservative measures to surgical interventions, such as total knee arthroplasty (TKA), the financial burden of TKA in many countries underscores the urgent need for effective conservative therapies. The pathophysiology of KOA involves articular cartilage degeneration, increased subchondral bone turnover, synovitis, and periarticular soft tissue contracture. Abnormal bone turnover, intensified by factors, such as weight gain and knee injury, precedes cartilage degeneration. Synovitis, characterized by inflammation in the synovial tissue, plays a crucial role in perpetuating the disease by triggering a cascade of catabolic and proinflammatory mediators, including cytokines, such as interleukin (IL)-1 beta, tumor necrosis factor-alpha, and IL-13. Periostin, an extracellular matrix protein, is implicated in KOA progression, with its levels increasing with disease severity. Materials & methods In this study, the preventive effect of boiogito (BOT), a traditional herbal medicine, on periostin secretion in human fibroblast-like synoviocytes (hFLS) stimulated by IL-13 was investigated. Synoviocyte Growth Medium and recombinant human IL-13 were used for cell culture and stimulation. BOT was dissolved in phosphate-buffered saline and applied to cell cultures. Periostin secretion and mRNA expression were measured using enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction, respectively. Cell viability was assessed using an MTT assay, and signal transducer and activator of transcription factor 6 (STAT6) phosphorylation was examined using Western blotting. Results IL-13 stimulation of hFLS significantly increased periostin secretion, with levels rising above 20 ng/mL after 72 h of stimulation. Pretreatment with BOT dose-dependently suppressed periostin secretion, with doses of 1,000 µg/mL significantly reducing periostin levels. Furthermore, BOT inhibited periostin mRNA expression and STAT6 phosphorylation in IL-13-stimulated hFLS, suggesting its potential in modulating IL-13-mediated inflammatory pathways in KOA. Conclusion This study demonstrated the preventive effect of BOT on periostin secretion in IL-13-stimulated hFLS, highlighting its potential as a therapeutic agent for KOA. By inhibiting periostin production and downstream signaling pathways, BOT may offer a promising conservative treatment option for KOA, addressing the inflammatory cascade implicated in disease progression. Further research is warranted to elucidate the specific herbal components responsible for the therapeutic effects of BOT and to validate its efficacy in clinical settings.

Duration of the preemptive analgesic effects of low- and high-frequency transcutaneous electrical nerve stimulation in rats with acute inflammatory pain.

Transcutaneous electrical nerve stimulation (TENS) activates various pathways to induce antinociceptive effects, based on the frequencies used. This study evaluates the preemptive analgesic effects and their duration of low- (LT: 4 Hz) and high-frequency TENS (HT: 100 Hz) using a rat model of acute inflammatory pain. Acute inflammation was induced by injecting 1% formalin into the hind paws of rats. LT or HT was applied for 30 min before formalin injection. Pain-related behaviors, such as licking, flinching, and lifting, were recorded for 60 min postinjection. Immunohistochemistry was used to assess the number of phosphorylated extracellular signal-regulated kinase (pERK)- and c-fos-positive cells in the spinal cord. Naloxone, a µ-opioid receptors (MORs) antagonist, and naltrindole, a δ-opioid receptors (DORs) antagonist, were administered before TENS application. Pain behavior duration and pERK- and c-fos-positive cell expression were then measured. LT and HT pretreatment significantly reduced both pain behaviors and the number of pERK- and c-fos-positive cells postformalin injection. Naloxone and naltrindole partially reversed the effects of LT and HT, respectively. Notably, HT's analgesic effect lasted up to 120 min whereas that of LT persisted for 90 min. LT and HT effectively exerted their preemptive analgesic effects on acute inflammatory pain by inhibiting pERK and c-fos expression in the spinal cord. HT presented a longer-lasting effect compared to LT. MOR and DOR activation may contribute to LT and HT's analgesic mechanisms, respectively.

Analgesic Effect of the Kampo Formula Yokukansan via the Suppression of Substance P in an Experimental Rat Model of Hunner-Type Interstitial Cystitis.

INTRODUCTION: Yokukansan (YKS), a Kampo formula used in traditional Japanese medicine, has an analgesic effect, and is used for various pain disorders. This study investigated its analgesic effects on Hunner-type interstitial cystitis (HIC) and its mechanism of action in animal models.   Methods: Rats with toll-like receptor-7 agonist (loxoribine)-induced HIC were used. Eight-week-old female Wistar rats were divided into three groups: control, HIC, and HIC-administered YKS (YKS + HIC). Bladder pain was assessed based on escape behavior using the von Frey test. Three days after HIC induction, the bladder and spinal cord were excised, and the expression of substance P (SP) was examined.   Results: The pain threshold decreased significantly in the HIC group compared to that in the control group, but this decrease was suppressed by further YKS administration. The expression of SP in the bladder wall and spinal cord increased significantly in the HIC group compared to that in the control group; however, this increase was suppressed by YKS administration. CONCLUSION: SP is involved in the onset of bladder pain via neurokinin 1 receptors in bladder tissue. YKS may be useful for managing HIC-induced pain, and the suppression of SP secretion is one of its mechanisms of action.

Effect and mechanism of aqueous extract of Chinese herbal prescription (TFK) in treating gout arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: With the rapid development of China's economic level, great changes have taken place in people's diet structure, gout has become a common disease that puzzles people's health, seriously affects the realization of China's "Healthy China" strategic goal. Gouty arthritis (GA) is a common joint disease caused by chronic purine metabolism disorder. Currently, drugs used to treat GA are allopurinol and colchicine. However, these drugs can only temporarily relieve the clinical symptoms of GA with significant side effects. More and more basic and clinical studies have confirmed that Traditional Chinese medicine has definite curative effect on GA. AIM OF THE STUDY: To elucidate the potential molecular mechanism of Tongfengkang (TFK) in the treatment of GA, and to provide experimental basis for the search and development of efficient and low-toxicity Chinese medicine for GA treatment. MATERIALS AND METHODS: Aqueous extract of TFK (AETFK) were determined by liquid phase high resolution mass spectrometry and the possible effective constituents were screened out. Acute GA model rats were established to detect the anti-inflammatory and detumification effects of AETFK on GA and explore the potential mechanism. The effect of AETFK on serum uric acid and urinary uric acid levels in acute GA rats was determined by automatic biochemical analyzer, and the effect of AETFK on the expression of acute GA-related immunoinflammatory factors were determined by protein thermal fluorescence chip. The effect of AETFK on the concentration of neutrophils in the joint fluid of acute GA rats were determined by Reichs-Giemsa staining. The effect of AETFK on macrophage activation was detected by ELISA. In order to further investigate the mechanism of AETFK in the treatment of GA, a rat model of hyperuricemia was established to detect the effect of AETFK on the level of uric acid in hyperuricemia model rats. Biochemical indexes of liver and kidney and hematoxylin-eosin staining (HE) were used to evaluate the effects of AETFK on the organs, and to preliminatively evaluate the safety of ventilation confufang. RESULTS: Compared with the model group, the joint swelling degree of GA rats in AETFK treatment group were significantly reduced, and the levels of blood uric acid and urine uric acid were also significantly decreased. Protein thermal fluorescence microarray results showed that the levels of gout - related inflammatory factors in GA rats in AETFK treatment group were significantly lower than those in control group. Reichsen-giemsa staining and ELISA showed that AETFK could reduce the activation of macrophages and the accumulation of neutrophils in the joint fluid. The results of liver and kidney biochemical indexes and HE staining showed that no obvious tissue damage was observed in the organs of rats treated with AETFK. CONCLUSIONS: AETFK not only has significant anti-inflammatory effects on GA, but also can significantly reduce the level of blood uric acid in GA rats, without obvious toxic and side effects. These effects may be related to AETFK's inhibition of neutrophil enrichment and macrophage activation during early inflammation.

Celastrus orbiculatus extract suppresses gastric cancer stem cells through the TGF-ß/Smad signaling pathway.

Cancer stem cells (CSCs) are the primary source of tumor recurrence and chemoresistance, which complicates tumor treatment and has a significant impact on poor patient prognosis. Therefore, the discovery of inhibitors that specifically target CSCs is warranted. Previous research has established that the TGF-ß/Smad signaling pathway is critical for the maintenance of CSCs phenotype, thus facilitating CSCs transformation. In this regard, Celastrus orbiculatus ethyl acetate extract (COE) was shown to exert anticancer properties; however, its therapeutic impact on gastric cancer stem cells (GCSCs) remains unknown. We here demonstrate that COE displayed a strong inhibitory effect on GCSCs growth and CSCs markers. Moreover, COE was shown to efficiently inhibit the development of tumor spheres and accelerate GCSCs apoptosis. Mechanistically, we established that COE could suppress the stemness phenotype of GCSCs by inhibiting the activity of the TGF-ß/Smad signaling pathway. To summarize, our data indicate that COE suppresses the malignant biological phenotype of GCSCs via the TGF-ß/Smad signaling pathway. These findings shed new light on the anticancer properties of COE and suggest new strategies for the development of efficient GCSCs therapeutics.

The Preventive Effects of Platelet-Rich Plasma Against Knee Osteoarthritis Progression in Rats.

BACKGROUND: In recent years, the intra-articular administration of platelet-rich plasma (PRP), a novel therapeutic strategy for knee osteoarthritis (KOA), has gained attention. However, the efficacy of PRP in inhibiting degenerative joint changes remains unclear. The current study aimed to evaluate the therapeutic effect of the intra-articular administration of PRP in rats with induced KOA. MATERIALS AND METHODS: PRP was prepared from the whole blood of nine-week-old male Wistar rats via centrifugation at 25°C, 200 × g, for seven minutes. KOA was induced in the right knees of the rats via destabilization of the medial meniscus (DMM) surgery. The animals were divided into the control, sham, DMM, and DMM + PRP groups (n = 5 each). The rats in the DMM + PRP group received 50 µL of intra-articular PRP in the right knee joint four weeks after surgery. The rotarod test was conducted to assess locomotive function. Eight weeks after DMM surgery, the degree of medial meniscus extrusion was measured via computed tomography (CT) images on the right knee. Then, a histological analysis of the harvested knees was conducted. KOA progression was assessed using the Osteoarthritis Research Society International (OARSI) score. The number of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in the subchondral bone was counted via histological analysis. RESULTS: The degree of medial meniscus extrusion did not significantly differ between the DMM and DMM + PRP groups. Similarly, there were no significant differences in the walking time based on the rotarod test between the DMM and DMM + PRP groups. However, the DMM group had a significantly higher OARSI score than the DMM + PRP group. The number of TRAP-positive osteoclasts in the subchondral bone of the DMM group increased over time, peaking four weeks after surgery. The DMM + PRP group had a higher number of TRAP-positive osteoclasts in the subchondral bone than the control group. However, there was no significant difference between the number of TRAP-positive osteoclasts between the DMM group and the control and sham groups. CONCLUSION: The intra-articular administration of PRP may inhibit KOA progression in a rat model, especially in the articular cartilage degradation and osteophyte formation. The results can provide further evidence about the efficacy of PRP against KOA progression and can contribute to the current practice of healthcare professionals based on accurate knowledge.

Multifactorial Comparative Analysis of Platelet-Rich Plasma and Serum Prepared Using a Commercially Available Centrifugation Kit.

Background Platelet-rich plasma (PRP) is an autologous product prepared by centrifuging whole blood. PRP is reported to have high tissue repair potential and anti-inflammatory properties. Recently, PRP has become a potential treatment option for osteoarthritis, contributing to pain relief and locomotive improvement. However, the underlying therapeutic mechanisms and key biochemical factors in PRP remain unclear. This study aimed to estimate the major factors for tissue repair involved in PRP treatment by comparing between serum and PRP prepared from the same patients using the Luminex assay. Methodology Blood samples were collected from nine healthy volunteers, and serum and PRP were prepared. PRP was prepared using a PEAK©ï¸Ž PRP SYSTEM kit of DePuy Synthes Mitek Sports Medicine (Raynham, Massachusetts, USA), which is a commercially available PRP preparation kit. The white blood cell count, hemoglobin level, and platelet count were automatically measured for both whole blood and PRP in the hospital's clinical laboratory using the XE-5000™ Automated Hematology System (Sysmex, Kobe, Japan). Comparative analysis of biological factors was then performed using the Luminex assay on serum and PRP. Results PRP was found to have significantly higher white blood cell and platelet counts and lower hemoglobin levels than whole blood. Furthermore, PRP contained significantly higher levels of various factors, including interleukin (IL)-1ra, IL-10, IL-13, C-C motif chemokine ligand (CCL)-2, CCL3, CCL4, CCL8, CCL13, CCL21, C-X-C motif chemokine ligand (CXCL)-10, matrix metalloproteinase (MMP)-3, MMP-9, cluster of differentiation (CD) 40 ligand, vascular endothelial growth factor (VEGF), VEGF-C, platelet-derived growth factor (PDGF)-AB, PDGF-BB, and bone morphogenic protein (BMP)-2. Additionally, IL-1ra and IL-4 showed significant correlations with white blood cell counts in PRP, whereas VEGF had a significant correlation with platelet counts. Conclusions PRP contains various factors in higher quantities than serum. Specifically, the notable increase in the anti-inflammatory cytokine IL-1ra is suggested to play a key role as a major therapeutic mechanism of PRP.

PTBP1 plays an important role in the development of gastric cancer.

BACKGROUND: Polypyrimidine tract binding protein 1 (PTBP1) has been found to play an important role in the occurrence and development of various tumors. At present, the role of PTBP1 in gastric cancer (GC) is still unknown and worthy of further investigation. METHODS: We used bioinformatics to analyze the expression of PTBP1 in patients with GC. Cell proliferation related experiments were used to detect cell proliferation after PTBP1 knockdown. Skeleton staining, scanning electron microscopy and transmission electron microscopy were used to observe the changes of actin skeleton. Proliferation and actin skeleton remodeling signaling pathways were detected by Western Blots. The relationship between PTBP1 and proliferation of gastric cancer cells was further detected by subcutaneous tumor transplantation. Finally, tissue microarray data from clinical samples were used to further explore the expression of PTBP1 in patients with gastric cancer and its correlation with prognosis. RESULTS: Through bioinformatics studies, we found that PTBP1 was highly expressed in GC patients and correlated with poor prognosis. Cell proliferation and cycle analysis showed that PTBP1 down-regulation could significantly inhibit cell proliferation. The results of cell proliferation detection related experiments showed that PTBP1 down-regulation could inhibit the division and proliferation of GC cells. Furthermore, changes in the morphology of the actin skeleton of cells showed that PTBP1 down-regulation inhibited actin skeletal remodeling in GC cells. Western Blots showed that PTBP1 could regulate proliferation and actin skeleton remodeling signaling pathways. In addition, we constructed PTBP1 Cas9-KO mouse model and performed xenograft assays to further confirm that down-regulation of PTBP1 could inhibit the proliferation of GC cells. Finally, tissue microarray was used to further verify the close correlation between PTBP1 and poor prognosis in patients with GC. CONCLUSIONS: Our study demonstrates for the first time that PTBP1 may affect the proliferation of GC cells by regulating actin skeleton remodeling. In addition, PTBP1 is closely related to actin skeleton remodeling and proliferation signaling pathways. We suppose that PTBP1 might be a potential target for the treatment of GC.

PTBP1 drives c-Myc-dependent gastric cancer progression and stemness.

BACKGROUND: Gastric cancer (GC) tumorigenesis and treatment failure are caused by cancer stem cells. Polypyrimidine tract binding protein 1 (PTBP1) was shown to be involved in the development of embryonic stem cells and is now being considered as a therapeutic target for tumour progression and stem-cell characteristics. METHODS: PTBP1 expression in GC samples was detected using tissue microarrays. Proliferation, colony formation, spheroid formation and stem-cell analysis were used to examine PTBP1's role in tumorigenesis and stem-cell maintenance. In AGS and HGC-27 cells with or without PTBP1 deficiency, ubiquitin-related protein expression and co-precipitation assays were performed. RESULTS: We identified that PTBP1 was aberrantly highly expressed and represented a novel prognostic factor in GC patients. PTBP1 maintained the tumorigenic activity and stem-cell characteristics of GC in vitro and in vivo. PTBP1 directly interacts with c-Myc and stabilises its protein levels by preventing its proteasomal degradation. This is mediated by upregulating the ubiquitin-specific proteases USP28 and limiting FBW7-mediated ubiquitination of c-Myc. Moreover, the depletion of PTBP1-caused tumour regression was significantly compromised by exogenous c-Myc expression. CONCLUSIONS: By preserving the stability of c-Myc through the ubiquitin-proteasome pathway, the oncogene PTBP1 supports stem-cell-like phenotypes of GC and is involved in GC progression.

Shoseiryuto Ameliorated TDI-Induced Allergic Rhinitis by Suppressing IL-33 Release from Nasal Epithelial Cells.

Toluene diisocyanate (TDI) is a major cause of occupational asthma and rhinitis. Shoseiryuto (SST) is one of the traditional herbal medicines (Kampo medicine) and has long been used as a natural medicine for allergic diseases such as allergic rhinitis (AR) and asthma. Recent studies have shown that the expression and release of IL-33, which regulates the TH2 cytokine response in epithelial cells, is an important step in developing the inflammatory response of the nasal mucosa. In this study, we investigated whether SST may ameliorate the TDI-induced AR-related symptoms in rats and inhibit IL-33 release from nasal epithelial cells. An AR rat model was generated by sensitization and induction with TDI. SST was administered during the sensitization period. AR-related symptoms in rats were evaluated, and IL-33 release was measured both in vivo and in vitro. SST suppressed symptoms appearing in TDI-induced AR model rats, such as elevated serum histamine and IL-33 levels in nasal lavage fluid (NLF)/serum, which were suppressed by SST administration. TDI-induced IL-33 release from the nasal epithelial cell nuclei was also observed and suppressed in SST-treated rats and cultured nasal epithelial cells. These results suggest that SST ameliorates the symptoms of TDI-induced AR at least partially by inhibiting IL-33 release from nasal epithelial cells.

Yokukansan Inhibits the Development of Morphine Tolerance by Regulating Presynaptic Proteins in DRG Neurons.

Opioids, such as morphine, are used in clinical settings for the management of acute and chronic pain. However, long-term use of morphine leads to antinociceptive tolerance and hypersensitivity. The cellular and molecular mechanisms of morphine tolerance seem to be quite complex, with suggestions including internalization of the µ-opioid receptor (MOR), neuroinflammation with activation of microglia and astrocytes, and changes in synaptic function in the central nervous system. Yokukansan (YKS), a traditional Kampo medicine consisting of seven herbs, has been used to treat emotional instability, neurosis, and insomnia. Interestingly, recent studies have begun to reveal the inhibitory effect of YKS on the development of morphine tolerance. In the present study, we determined the effect of YKS on morphine tolerance formation and its mechanisms in a rat model, focusing on the synapses between primary sensory neurons and spinal dorsal horn secondary neurons. We found that morphine tolerance formation was significantly inhibited by YKS (0.3 or 1.0 g/kg/day) preadministration for 7 days. Repeated administration of morphine (10 mg/kg/day) increased the expression of presynaptic proteins, including synaptotagmin I, in the spinal cord, which was suppressed by YKS. Furthermore, these changes in presynaptic protein expression were more pronounced at isolectin B4 (IB4)-positive excitatory synapses around the lamina II of the dorsal horn. These results suggest that YKS suppresses the development of morphine tolerance by inhibiting the enhancement of presynaptic function of dorsal root ganglia neurons projecting to spinal dorsal horn neurons caused by continuous morphine administration.

The Japanese Herbal Medicine Yokukansan Exerted Antioxidant and Analgesic Effects in an Experimental Rat Model of Hunner-Type Interstitial Cystitis.

Background and Objectives: The Japanese herbal medicine Yokukansan (YKS) has analgesic properties and is used for various pain disorders. The purpose of the present study was to investigate the effects of YKS in Hunner-type interstitial cystitis (HIC) using an experimental rat model of HIC and to explore its antioxidant activity and role as the underlying mechanism of action. Materials and Methods: The antioxidant capacity of YKS was evaluated by determining its hydroxyl radical (·OH) scavenging capacity using electron spin resonance (ESR). Next, the effects of YKS administration were explored using a toll-like receptor-7 agonist-induced rat model of HIC. The von Frey test was performed to assess bladder pain. Three days after HIC induction, the bladder was removed, and the expression of oxidative stress parameters in the bladder wall was investigated (reactive oxygen metabolites (ROMs), ·OH, and 8-hydroxy-2'-deoxyguanosine (8-OhdG)). Results: YKS had a ·OH scavenging capacity according to the ESR study. In the von Frey test, a significant decrease in the withdrawal threshold was observed in the HIC group compared with the control group; however, the decrease was ameliorated by the administration of YKS. Oxidative stress parameters showed increasing tendencies (ROMs test and 8-OHdG) or a significant increase (·OH) in the HIC group compared with the control group; however, the increase was significantly suppressed by the administration of YKS. Conclusions: These findings suggest that YKS is effective against HIC and that its antioxidant activity is involved in the mechanism of action.

Kamikihito rescued depressive-like behaviors and hippocampus neurogenesis in chronic restraint stress rats.

Background and aim: Substantial evidence suggests the effectiveness of plant-based medicine in stress-related diseases. Kamikihito (KKT), a Japanese traditional herbal medicine (Kampo), has been used for anemia, insomnia, and anxiety. Recent studies revealed its ameliorating effect on cognitive and memory dysfunction in several animal models. We, therefore, determined whether daily supplementation of KKT has an antidepressant-like effect on the stress-induced behavioral and neurological changes in rats. Experimental procedure: The effect of KKT against the stress-induced changes in anxiety- and depressive-like behaviors and hippocampal neurogenesis were determined using a rat model of chronic restraint stress (CRS). KKT was orally administered daily at 300 or 1000 mg/kg during 21 consecutive days of CRS (6 h/day). The effect of CRS and KKT on physiological parameters, including body weight gain, food/water consumptions, plasma corticosterone (CORT) levels, and percentage of adrenal gland weight to body weight, were firstly measured. Anxiety- and depressive-like behaviors in rats were assessed in the open field test (OFT), sucrose preference test (SPT), and forced swimming test (FST). Hippocampal neurogenesis was determined by immunohistochemistry. Results and conclusion: CRS for 21 days caused a significant decrease in body weight gain and increase in plasma CORT levels and percentage of adrenal gland weight to body weight, which were rescued by KKT treatment. KKT also suppressed the CRS-induced anxiety- and depressive-like behaviors and impairment of hippocampal neurogenesis. These results suggest that daily treatment of KKT has a protective effect against physiological, neurological, and behavioral changes in a rat model of depression.

Corrigendum: The Ethyl Acetate Extract From Celastrus Orbiculatus Promotes Apoptosis of Gastric Cancer Cells Through Mitochondria Regulation by PHB.

[This corrects the article DOI: 10.3389/fphar.2021.635467.].

[Corrigendum] DJ­1 promotes cell proliferation and tumor metastasis in esophageal squamous cell carcinoma via the Wnt/ß­catenin signaling pathway.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that a pair of data panels featured between Figs. 4 and 7 contained overlapping data such that the data were derived from the same original source where they were intending to depict the results from experiments performed under different experimental conditions, and a pair of the data panels featured in Fig. 8 for the ß­catenin data also appeared to show overlapping data. The authors were able to re­examine their original data, and have identified the data that were intended to have been shown for these figure parts. The corrected versions of Fig. 4 (showing the correct data for the LV­DJ­1/migration experiment in Fig. 4A), Fig. 7 (showing the correct data for the LV­DJ­1 + XAV939/migration experiment) and Fig. 8 (showing the correct data for the LV­siRNA­DJ­1 experiment) are shown on the subsequent pages. The authors confirm that these inadvertent errors did not have any major impact on the conclusions reported in their paper, are grateful to the Editor of International Journal of Oncology for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in International Journal of Oncology 56: 1115­1128, 2020; DOI: 10.3892/ijo.2020.5005].

Celastrol Inhibits the Proliferation and Decreases Drug Resistance of Cisplatin- Resistant Gastric Cancer SGC7901/DDP Cells.

BACKGROUND: This study aimed to determine the effect and mechanism of Celastrol inhibiting the proliferation and decreasing the drug resistance of cisplatin-resistant gastric cancer cells. OBJECTIVE: The objective of this study was to explore the effect and mechanism of Celastrol on proliferation and drug resistance of human gastric cancer cisplatin-resistant cells SGC7901/DDP. METHODS: The thiazole blue (MTT) method was used to detect the sensitivity of human gastric cancer cisplatinresistant cells SGC7901/DPP to cisplatin and Celastrol to determine the Drug Resistance Index (DRI). According to the half Inhibitory Concentration (IC50) value, the action of the concentration of the following experimental drugs was set to reduce the cytotoxicity. Annexin V-FITC/PI double staining method was used to detect the apoptosis of SGC7901/DDP cells induced by Celastrol. Western Blot was used to examine the expression levels of P-glycoprotein (P-gp), Multidrug Resistance Associated Protein 1 (MRP1), Breast Cancer Resistance Associated Protein (Breast Cancer Resistance)-relative protein (BCRP), and mechanistic Target of Rapamycin (mTOR) pathway-related proteins. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression levels of P-gp, MRP1, and BCRP. RESULTS: (1) Compared with the control group (we set the untreated group as the control group), the proliferation of the SGC7901/DPP cells was significantly inhibited after treating with 0.1-6.4µmol/L Celastrol in a time- and concentration-dependent manner (P<0.05). The Drug Resistance Index (DRI) of the SGC7901/DPP cells to DDP was 5.64. (2) Compared with the control group, Celastrol could significantly inhibit the proliferation and induce the apoptosis of the SGC7901/DPP cells (P<0.05). (3) The mRNA and protein expression levels of P-gp, MRP1, and BCRP in the SGC7901/DPP cells were significantly higher than those in the SGC7901 cells. However, after treating with Celastrol, the expression levels of P-gp, MRP1, and BCRP in the SGC7901/DPP cells were significantly reduced (P<0.05). (4) Compared with the control group, the Celastrol treatment also reduced the expression of the mTOR signaling pathway-related proteins, suggesting that the mTOR signaling pathway may be involved in the process of Celastrol inhibiting the proliferation of the SGC7901/DDP cells and reducing their drug resistance. (5) Significantly, the combination of Celastrol and DDP reduced the expression of P-gp, MRP1, and BCRP in the SGC7901/DPP cells. CONCLUSION: Celastrol can inhibit the proliferation of the SGC7901/DDP cells, induce their apoptosis, and reduce the expression of drug resistance genes, probably by inhibiting the expression of the proteins related to the mTOR signaling pathway.

Kampo Formulae for the Treatment of Neuropathic Pain ∼ Especially the Mechanism of Action of Yokukansan ∼.

Kampo medicine has been practiced as traditional medicine (TM) in Japan. Kampo medicine uses Kampo formulae that are composed of multiple crude drugs to make Kampo formulae. In Japan, Kampo formulae are commonly used instead of or combined with Western medicines. If drug therapy that follows the guidelines for neuropathic pain does not work or cannot be taken due to side effects, various Kampo formulae are considered as the next line of treatment. Since Kampo formulae are composed of two or more kinds of natural crude drugs, and their extracts contain many ingredients with pharmacological effects, one Kampo formula usually has multiple effects. Therefore, when selecting a formula, we consider symptoms other than pain. This review outlines the Kampo formulae that are frequently used for pain treatment and their crude drugs and the basic usage of each component. In recent years, Yokukansan (YKS) has become one of the most used Kampo formulae for pain treatment with an increasing body of baseline research available. We outline the known and possible mechanisms by which YKS exerts its pharmacologic benefits as an example of Kampo formulae's potency and holistic healing properties.

Brain-derived neurotrophic factor predominantly regulates the expression of synapse-related genes in the striatum: Insights from in vitro transcriptomics.

AIM: The striatum, a main component of the basal ganglia, is a critical part of the motor and reward systems of the brain. It consists of GABAergic and cholinergic neurons and receives projections of dopaminergic, glutamatergic, and serotonergic neurons from other brain regions. Brain-derived neurotrophic factor (BDNF) plays multiple roles in the central nervous system, and striatal BDNF has been suggested to be involved in psychiatric and neurodegenerative disorders. However, the transcriptomic impact of BDNF on the striatum remains largely unknown. In the present study, we performed transcriptomic profiling of striatal cells stimulated with BDNF to identify enriched gene sets (GSs) and their novel target genes in vitro. METHODS: We carried out RNA sequencing (RNA-Seq) of messenger RNA extracted from primary dissociated cultures of rat striatum stimulated with BDNF and conducted Generally Applicable Gene-set Enrichment (GAGE) analysis on 10599 genes. Significant differentially expressed genes (DEGs) were determined by differential expression analysis for sequence count data 2 (DESeq2). RESULTS: GAGE analysis identified significantly enriched GSs that included GSs related to regulation and dysregulation of synaptic functions, such as synaptic vesicle cycle and addiction to nicotine and morphine, respectively. It also detected GSs related to various types of synapses, including not only GABAergic and cholinergic synapses but also dopaminergic and glutamatergic synapses. DESeq2 revealed 72 significant DEGs, among which the highest significance was observed in the apolipoprotein L domain containing 1 (Apold1). CONCLUSIONS: The present study indicates that BDNF predominantly regulates the expression of synaptic-function-related genes and that BDNF promotes synaptogenesis in various subtypes of neurons in the developing striatum. Apold1 may represent a unique target gene of BDNF in the striatum.