• The Korean Journal of Pain
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• v.36 no.4
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• pp.408-424
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• 2023

Central post-stroke pain (CPSP) is an incapacitating disorder that impacts a substantial proportion of stroke survivors and can diminish their quality of life. Conventional therapies for CPSP, including tricyclic antidepressants, anticonvulsants, and opioids, are frequently ineffective, necessitating the investigation of alternative therapeutic strategies. Repetitive transcranial magnetic stimulation (rTMS) is now recognized as a promising noninvasive pain management method for CPSP. rTMS modulates neural activity through the administration of magnetic pulses to specific cortical regions. Trials analyzing the effects of rTMS on CPSP have generated various outcomes, but the evidence suggests possible analgesic benefits. In CPSP and other neuropathic pain conditions, high-frequency rTMS targeting the primary motor cortex (M1) with figure-eight coils has demonstrated significant pain alleviation. Due to its associaton with analgesic benefits, M1 is the most frequently targeted area. The duration and frequency of rTMS sessions, as well as the stimulation intensity, have been studied in an effort to optimize treatment outcomes. The short-term pain relief effects of rTMS have been observed, but the long-term effects (> 3 months) require further investigation. Aspects such as stimulation frequency, location, and treatment period can influence the efficacy of rTMS and ought to be considered while planning the procedure. Standardized guidelines for using rTMS in CPSP would optimize therapy protocols and improve patient outcomes. This review article provides an up-to-date overview of the incidence, clinical characteristics, outcome of rTMS in CPSP patients, and future perspective in the field.

• Journal of Korean Dental Science
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• v.16 no.1
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• pp.9-22
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• 2023

Xerostomia is defined as the subjective complaint of dry mouth with or without hyposalivation, which is insufficient salivary secretion from salivary gland. Xerostomia can lead to multiple oral symptoms such as dental caries, halitosis, burning mouth syndrome, and oral candidiasis, which can significantly impact the well-being of patients, especially in geriatric patients who may already have compromised health. Clinical findings of xerostomia include decreased salivary flow and alterations in salivary composition. These changes can lead to various oral health problems such as dental caries, periodontitis, swallowing and speaking difficulties, taste disturbances, halitosis, mucosal diseases, and burning mouth syndrome. Recognizing these clinical manifestations is essential for early diagnosis and appropriate management. Although several reasons and risk factors have been suggested for xerostomia such as aging, chemo-radiation therapy, systemic disease, and Sjögren's syndrome, the polypharmacy is recently highlighted especially in elderly patients. Understanding the etiology and risk factors associated with xerostomia is crucial for effective management. To manage xerostomia patients, a multidisciplinary guideline should be established beyond dental care. Through this literature review, we summarized consideration for diagnostic, therapeutic, nursing essentials for the clinical guideline. By addressing the underlying causes and implementing appropriate treatment strategies, healthcare professionals can improve the quality of life for individuals suffering from xerostomia.

• Journal of Chest Surgery
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• v.56 no.5
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• pp.353-358
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• 2023

Background: Malignant pleural effusion affects many patients with advanced cancer. When chemotherapy or radiotherapy fails to relieve malignant pleural effusion and related symptoms, drainage and pleurodesis can help. Although surgical talc pleurodesis is the most widely used method, Viscum album, which has been recently used in surgical or bedside procedures, has demonstrated significant results and is as effective as talc. This study aimed to determine the most effective agent and procedure. Methods: Between January 2015 and July 2022, chemical pleurodesis was performed in 137 patients with malignant pleural effusion, using a V. album surgical procedure in 48, a V. album bedside procedure in 55, and a talc surgical procedure in 34 patients. We reviewed patients' clinical responses and disease progression after chemical pleurodesis. Results: The success rate was not significantly different among the V. album surgical procedures (91.7%), V. album bedside procedures (83.6%), and talc surgical procedures (91.2%). However, the total drainage amount and tube insertion duration in both Viscum groups were more effective than those in the talc group. Furthermore, the bedside Viscum group showed significantly lower post-pleurodesis pain scores than the other 2 groups. Conclusion: According to our results, talc and V. album can be considered ideal agents for chemical pleurodesis. However, Viscum pleurodesis showed safer outcomes in terms of ensuring quality of life than talc. Additionally, the bedside Viscum group showed significantly lower pain scores than the other groups. Hence, patients for whom surgical procedures are inappropriate can undergo bedside Viscum pleurodesis without diminishing the therapeutic effect.

• Biomolecules & Therapeutics
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• v.31 no.5
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• pp.515-525
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• 2023

The most common heart valve disorder is calcific aortic valve stenosis (CAVS), which is characterized by a narrowing of the aortic valve. Treatment with the drug molecule, in addition to surgical and transcatheter valve replacement, is the primary focus of researchers in this field. The purpose of this study is to determine whether niclosamide can reduce calcification in aortic valve interstitial cells (VICs). To induce calcification, cells were treated with a pro-calcifying medium (PCM). Different concentrations of niclosamide were added to the PCM-treated cells, and the level of calcification, mRNA, and protein expression of calcification markers was measured. Niclosamide inhibited aortic valve calcification as observed from reduced alizarin red s staining in niclosamide treated VICs and also decreased the mRNA and protein expressions of calcification-specific markers: runt-related transcription factor 2 and osteopontin. Niclosamide also reduced the formation of reactive oxygen species, NADPH oxidase activity and the expression of Nox2 and p22^phox. Furthermore, in calcified VICs, niclosamide inhibited the expression of β-catenin and phosphorylated glycogen synthase kinase (GSK-3β), as well as the phosphorylation of AKT and ERK. Taken together, our findings suggest that niclosamide may alleviate PCM-induced calcification, at least in part, by targeting oxidative stress mediated GSK-3β/β-catenin signaling pathway via inhibiting activation of AKT and ERK, and may be a potential treatment for CAVS.

• Biomolecules & Therapeutics
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• v.31 no.5
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• pp.550-558
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• 2023

Hair loss is a common condition that can have a negative impact on an individual's quality of life. The severe side effects and the low efficacy of current hair loss medications create unmet needs in the field of hair loss treatment. Hyaluronan and Proteoglycan Link Protein 1 (HAPLN1), one of the components of the extracellular matrix, has been shown to play a role in maintaining its integrity. HAPLN1 was examined for its ability to impact hair growth with less side effects than existing hair loss treatments. HAPLN1 was predominantly expressed in the anagen phase in three stages of the hair growth cycle in mice and promotes the proliferation of human hair matrix cells. Also, recombinant human HAPLN1 (rhHAPLN1) was shown to selectively increase the levels of transforming growth factor-β receptor II in human hair matrix cells. Furthermore, we observed concomitant activation of the ERK1/2 signaling pathway following treatment with rhHAPLN1. Our results indicate that rhHAPLN1 elicits its cell proliferation effect via the TGF-β2-induced ERK1/2 pathway. The prompt entering of the hair follicles into the anagen phase was observed in the rhHAPLN1-treated group, compared to the vehicle-treated group. Insights into the mechanism underlying such hair growth effects of HAPLN1 will provide a novel potential strategy for treating hair loss with much lower side effects than the current treatments.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.27-39
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• 2023

Extensive research supported the therapeutic potential of curcumin, a naturally occurring compound, as a promising cytokine-suppressive anti-inflammatory drug. This study aimed to investigate the synergistic anti-inflammatory and anti-cytokine activities by combining 6-shogaol and 10-shogaol to curcumin, and associated mechanisms in modulating lipopolysaccharides and interferon-γ-induced proinflammatory signaling pathways. Our results showed that the combination of 6-shogaol-10-shogaolcurcumin synergistically reduced the production of nitric oxide, inducible nitric oxide synthase, tumor necrosis factor and interlukin-6 in lipopolysaccharides and interferon-γ-induced RAW 264.7 and THP-1 cells assessed by the combination index model. 6-shogaol-10-shogaol-curcumin also showed greater inhibition of cytokine profiling compared to that of 6-shogaol-10-shogaol or curcumin alone. The synergistic anti-inflammatory activity was associated with supressed NFκB translocation and downregulated TLR4-TRAF6-MAPK signaling pathway. In addition, SC also inhibited microRNA-155 expression which may be relevant to the inhibited NFκB translocation. Although 6-shogaol-10-shogaol-curcumin synergistically increased Nrf2 activity, the anti-inflammatory mechanism appeared to be independent from the induction of Nrf2. 6-shogaol-10-shogaol-curcumin provides a more potent therapeutic agent than curcumin alone in synergistically inhibiting lipopolysaccharides and interferon-γ induced proinflammatory mediators and cytokine array in macrophages. The action was mediated by the downregulation of TLR4/TRAF6/MAPK pathway and NFκB translocation.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.40-47
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• 2023

Activation of the NLRP3 inflammasome is a necessary process to induce fibrosis in nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH) is a kind of NAFLD that encompasses the spectrum of liver disease. It is characterized by inflammation and ballooning of hepatocytes during steatosis. We tested whether inhibiting the NLRP3 inflammasome could prevent the development and pathology of NASH. We identified loganin as an inhibitor of the NLRP3 inflammasome and investigated whether in vivo administration of loganin prevented NASH symptoms using a methionine-choline deficient (MCD) diet model in mice. We found that loganin inhibited the NLRP3 inflammasome activation triggered by ATP or nigericin, as shown by suppression of the production of interleukin (IL)-1β and caspase-1 (p10) in mouse primary macrophages. The speck formation of apoptosisassociated speck-like protein containing a caspase recruitment domain (ASC) was blocked by loganin, showing that the assembly of the NLRP3 inflammasome complex was impaired by loganin. Administration of loganin reduced the clinical signs of NASH in mice fed the MCD diet, including hepatic inflammation, fat accumulation, and fibrosis. In addition, loganin reduced the expression of NLRP3 inflammasome components in the liver. Our findings indicate that loganin alleviates the inflammatory symptoms associated with NASH, presumably by inhibiting NLRP3 inflammasome activation. In summary, these findings imply that loganin may be a novel nutritional and therapeutic treatment for NASH-related inflammation.

• Journal of Gastric Cancer
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• v.23 no.2
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• pp.328-339
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• 2023

Purpose: This study aimed to evaluate the efficacy and safety of neoadjuvant programmed cell death-1 (PD-1) inhibitors plus apatinib and chemotherapy (PAC) in patients with locally advanced gastric cancer (LAGC). Materials and Methods: Seventy-three patients with resectable LAGC were enrolled and named the PAC group (n=39) or apatinib plus chemotherapy (AC) group (n=34) based on the treatment they chose. Neoadjuvant therapy was administered in a 21-day cycle for 3 consecutive cycles, after which surgery was performed. Results: The PAC group exhibited a higher objective response rate than the AC group (74.4% vs. 58.8%, P=0.159). Moreover, the PAC group showed a numerically better response profile than the AC group (P=0.081). Strikingly, progression-free survival (PFS) (P=0.019) and overall survival (OS) (P=0.049) were prolonged, whereas disease-free survival (DFS) tended to be longer in the PAC group than in the AC group (P=0.056). Briefly, the 3-year PFS, DFS, and OS rates were 76.1%, 76.1%, and 86.7% in the PAC group and 46.9%, 49.9%, and 70.3% in the AC group, respectively. Furthermore, PAC (vs. AC) treatment (hazard ratio=0.286, P=0.034) was independently associated with prolonged PFS in multivariate Cox regression analyses. The incidence of adverse events did not differ between the two groups (all P>0.05), where leukopenia, anemia, hypertension, and other adverse events were commonly observed in the PAC group. Conclusions: Neoadjuvant PAC therapy may achieve a preferable pathological response, delayed progression, and prolonged survival compared to AC therapy with a similar safety profile in patients with LAGC; however, further validation is warranted.

• Journal of Dental Anesthesia and Pain Medicine
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• v.23 no.2
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• pp.69-81
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• 2023

Background: In order to assess the effectiveness of various analgesio-sedative combinations for pain relief and sedation in pediatric dental patients, a thorough evaluation of clinical studies and patient outcomes is necessary. Methods: A total of 128 healthy, uncooperative pediatric dental patients were randomly allocated to receive one of the four combinations of drugs via the intranasal (IN) route: Group I received midazolam-ketamine (MK), Group II received dexmedetomidine-ketamine (DK), Group III received midazolam-fentanyl (MF), and Group IV received dexmedetomidine-fentanyl (DF) in a parallel-arm study design. The efficacy and safety of the combinations were evaluated using different parameters. Results: The onset of sedation was significantly faster in the DF group than in the DK, MF, and MK groups (P < 0.001). The depth of sedation was significantly higher in the DK and DF groups than in the MK and MF groups (P < 0.01). DK and DF produced significant intra- and postoperative analgesia when compared with combinations of MK and MF. No significant adverse events were observed for any of the combinations. Conclusions: The DK and DF groups showed potential as analgesio-sedatives in view of their anxiolytic and analgesic effects.

• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.126-136
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• 2022

Liver fibrosis is part of the wound healing process to help the liver recover from the injuries caused by various liver-damaging insults. However, liver fibrosis often progresses to life-threatening cirrhosis and hepatocellular carcinoma. To overcome the limitations of current in vivo liver fibrosis models for studying the pathophysiology of liver fibrosis and establishing effective treatment strategies, we developed a new mouse model of liver fibrosis using polyhexamethylene guanidine phosphate (PHMG-p), a humidifier sterilizer known to induce lung fibrosis in humans. Male C57/BL6 mice were intraperitoneally injected with PHMG-p (0.03% and 0.1%) twice a week for 5 weeks. Subsequently, liver tissues were examined histologically and RNA-sequencing was performed to evaluate the expression of key genes and pathways affected by PHMG-p. PHMG-p injection resulted in body weight loss of ~15% and worsening of physical condition. Necropsy revealed diffuse fibrotic lesions in the liver with no effect on the lungs. Histology, collagen staining, immunohistochemistry for smooth muscle actin and collagen, and polymerase chain reaction analysis of fibrotic genes revealed that PHMG-p induced liver fibrosis in the peri-central, peri-portal, and capsule regions. RNA-sequencing revealed that PHMG-p affected several pathways associated with human liver fibrosis, especially with upregulation of lumican and IRAK3, and downregulation of GSTp1 and GSTp2, which are closely involved in liver fibrosis pathogenesis. Collectively we demonstrated that the PHMG-p-induced liver fibrosis model can be employed to study human liver fibrosis.