Pattern of pericardial calcification determines mid-term postoperative outcomes after pericardiectomy in chronic constrictive pericarditis.

OBJECTIVES: Although pericardiectomy is an effective treatment for constrictive pericarditis (CP), clinical outcomes are not always successful. Pericardial calcification is a unique finding in CP, although the amount and localization of calcification can vary. We investigated how the pattern and amount of pericardial calcification affect mid-term postoperative outcomes after pericardiectomy to treat CP. METHODS: All patients of total pericardiectomy in our hospital from 2010 to 2020 were enrolled. Preoperative Computed tomography (CT) scans of 98 consecutive patients were available and analyzed. Medical records were reviewed retrospectively. Cardiovascular events were defined as cardiovascular death or hospitalization associated with a heart failure symptom, and all-cause events were defined as any event that required admission. CT scans were analyzed, and the volume and localization pattern of peri-calcification were determined. Pericardium calcium scores are presented using Agatston scores. RESULTS: Of the 98 patients, 25 (25.5%) were hospitalized with heart failure symptoms after pericardiectomy. The median follow-up duration for all patients was 172 weeks. The group with a cardiovascular event had a lower calcium score than patients without an event. Multivariate Cox proportional analysis showed that high ln(calcium score+1) before pericardiectomy was a dependent predictor of cardiovascular event (hazard ratio, 0.90; p = 0.04) after pericardiectomy. When we set the cut-off value (ln(calcium score+1) = 7.22), there was a significant difference in cardiovascular events in the multivariate Cox proportional analysis (p = 0.04). CONCLUSION: A low burden of pericardial calcification was associated with a high rate of mid-term clinical events after pericardiectomy to treat CP.

Magnolin Inhibits Paclitaxel-Induced Cold Allodynia and ERK1/2 Activation in Mice.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of anti-cancer drugs. The main symptoms often include sensory disturbances and neuropathic pain, and currently there is no effective treatment for this condition. This study aimed to investigate the suppressive effects of magnolin, an extracellular signal-regulated kinase (ERK) inhibitor substance derived from a 95% EtOH extract of the seeds of Magnolia denudata, on the symptoms of CIPN. A taxol-based anti-cancer drug paclitaxel (PTX) was repeatedly injected (2 mg/kg/day, total 8 mg/kg) into mice to induce CIPN. A neuropathic pain symptom was assessed using a cold allodynia test that scores behaviors of licking and shaking paw after plantar administration of acetone drop. Magnolin was administered intraperitoneally (0.1, 1, or 10 mg/kg) and behavioral changes to acetone drop were measured. The effect of magnolin administration on ERK expression in the dorsal root ganglion (DRG) was investigated using western blot analysis. The results showed that the repeated injections of PTX induced cold allodynia in mice. Magnolin administration exerted an analgesic effect on the PTX-induced cold allodynia and inhibited the ERK phosphorylation in the DRG. These results suggest that magnolin could be developed as an alternative treatment to suppress paclitaxel-induced neuropathic pain symptoms.

Pear pomace alleviated atopic dermatitis in NC/Nga mice and inhibited LPS-induced inflammation in RAW 264.7 macrophages.

BACKGROUND/OBJECTIVES: Poorly regulated inflammation is believed to be the most predominant factor that can result in a wide scope of diseases including atopic dermatitis (AD). Despite many studies on the effect of pear pomace in obesity-related disorders including dysregulated gut microbiota, the protective effect of pear pomace in AD is still unknown. This study aimed to evaluate the effect of pear pomace ethanol extract (PPE) on AD by inhibiting inflammation. MATERIALS/METHODS: In the in vivo experiment, 2, 4-dinitrochlorobenzene (DNCB) was applied to NC/Nga mice to induce AD-like skin lesions. After the induction, PPE was administered daily by oral gavage for 4 weeks. The clinical severity score, serum IgE levels, spleen weight, histological changes in dorsal skin, and inflammation-related proteins were measured. In the cell study, RAW 264.7 cells were pretreated with PPE before stimulation with lipopolysaccharide (LPS). Nitrite oxide (NO) production and nuclear factor kappa B (NF-kB) protein expression were detected. RESULTS: Compared to the AD control (AD-C) group, IgE levels were dramatically decreased via PPE treatment. PPE significantly reduced scratching behavior, improved skin symptoms, and decreased ear thickness compared to the AD-C group. In addition, PPE inhibited the DNCB-induced expression of inducible nitrite oxide synthase (iNOS), the receptor for advanced glycation end products, extracellular signal-regulated kinase (ERK) 1/2, and NF-κB. PPE inhibited the LPS-induced overproduction of NO and the enhanced expression of iNOS and cyclooxygenase-2. Moreover, the phosphorylation of ERK1/2 and NF-κB in RAW 264.7 cells was suppressed by PPE. CONCLUSIONS: These results suggest that PPE could be explored as a therapeutic agent to prevent AD.

Red Pepper Seeds Inhibit Hepatic Lipid Accumulation by Inducing Autophagy via AMPK Activation.

Although the red pepper and its seeds have been studied for metabolic diseases, the effects and potential mechanisms of red pepper seed extract (RPS) on hepatic lipid accumulation are not yet completely understood. This study aimed to evaluate the inhibitory effect of RPS on hepatic lipid accumulation via autophagy. C57BL/6 mice were fed a high-fat diet (HFD) or a HFD supplemented with RPS. RPS treatment inhibited hepatic lipid accumulation by suppressing lipogenesis, inducing hepatic autophagic flux, and activating AMPK in HFD-fed mice. To investigate the effect of RPS on an oleic acid (OA)-induced hepatic steatosis cell model, HepG2 cells were incubated in a high-glucose medium and OA, followed by RPS treatment. RPS treatment decreased OA-induced lipid accumulation and reduced the expression of lipogenesis-associated proteins. Autophagic flux dramatically increased in the RPS-treated group. RPS phosphorylated AMPK in a dose-dependent manner, thereby dephosphorylated mTOR. Autophagy inhibition with 3-methyladenine (3-MA) antagonized RPS-induced suppression of lipogenesis-related protein expressions. Moreover, the knockdown of endogenous AMPK also antagonized the RPS-induced regulation of lipid accumulation and autophagy. Our findings provide new insights into the beneficial effects of RPS on hepatic lipid accumulation through the AMPK-dependent autophagy-mediated downregulation of lipogenesis.

Can Panax ginseng help control cytokine storm in COVID-19?

Coronavirus disease 2019 (COVID-19) is currently a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 are directly associated with hyper-activation of innate immune response that excessively produce pro-inflammatory cytokines and induce cytokine storm, leading to multi-organ-failure and significant morbidity/mortality. Currently, several antiviral drugs such as Paxlovid (nirmatrelvir and ritonavir) and molnupiravir are authorized to treat mild to moderate COVID-19, however, there are still no drugs that can specifically fight against challenges of SARS-CoV-2 variants. Panax ginseng, a medicinal plant widely used for treating various conditions, might be appropriate for this need due to its anti-inflammatory/cytokine/viral activities, fewer side effects, and cost efficiency. To review Panax ginseng and its pharmacologically active-ingredients as potential phytopharmaceuticals for treating cytokine storm of COVID-19, articles that reporting its positive effects on the cytokine production were searched from academic databases. Experimental/clinical evidences for the effectiveness of Panax ginseng and its active-ingredients in preventing or mitigating cytokine storm, especially for the cascade of cytokine storm, suggest that they might be beneficial as an adjunct treatment for cytokine storm of COVID-19. This review may provide a new approach to discover specific medications using Panax ginseng to control cytokine storm of COVID-19.

Rg3-enriched Korean Red Ginseng extract inhibits blood-brain barrier disruption in an animal model of multiple sclerosis by modulating expression of NADPH oxidase 2 and 4.

BACKGROUND: Multiple sclerosis (MS) and its animal model, the experimental autoimmune encephalomyelitis (EAE), are primarily characterized as dysfunction of the blood-brain barrier (BBB). Ginsenoside-Rg3-enriched Korean Red Ginseng extract (Rg3-KRGE) is known to exert neuroprotective, anti-inflammatory, and anti-oxidative effects on neurological disorders. However, effects of Rg3-KRGE in EAE remain unclear. METHODS: Here, we investigated whether Rg3-KRGE may improve the symptoms and pathological features of myelin oligodendroglial glycoprotein (MOG)35-55 peptide - induced chronic EAE mice through improving the integrity of the BBB. RESULTS: Rg3-KRGE decreased EAE score and spinal demyelination. Rg3-KRGE inhibited Evan's blue dye leakage in spinal cord, suppressed increases of adhesion molecule platelet endothelial cell adhesion molecule-1, extracellular matrix proteins fibronection, and matrix metallopeptidase-9, and prevented decreases of tight junction proteins zonula occludens-1, claudin-3, and claudin-5 in spinal cord following EAE induction. Rg3-KRGE repressed increases of proinflammatory transcripts cyclooxygenase-2, inducible nitric oxide synthase, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-alpha, but enhanced expression levels of anti-inflammatory transcripts arginase-1 and IL-10 in the spinal cord following EAE induction. Rg3-KRGE inhibited the expression of oxidative stress markers (MitoSOX and 4-hydroxynonenal), the enhancement of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and NOX4, and NADPH activity in the spinal cord of chronic EAE mice. Furthermore, apocynin, a NOX inhibitor, mimicked beneficial effects of Rg3-KRGE in chronic EAE mice. CONCLUSION: Our findings suggest that Rg3-KRGE might alleviate behavioral symptoms and pathological features of MS by improving BBB integrity through modulation of NOX2/4 expression.

Statistical Analysis of Treatment Planning Parameters for Prediction of Delivery Quality Assurance Failure for Helical Tomotherapy.

PURPOSE: This study aimed to investigate the parameters with a significant impact on delivery quality assurance (DQA) failure and analyze the planning parameters as possible predictors of DQA failure for helical tomotherapy. METHODS: In total, 212 patients who passed or failed DQA measurements were retrospectively included in this study. Brain (n = 43), head and neck (n = 37), spinal (n = 12), prostate (n = 36), rectal (n = 36), pelvis (n = 13), cranial spinal irradiation and a treatment field including lymph nodes (n = 24), and other types of cancer (n = 11) were selected. The correlation between DQA results and treatment planning parameters were analyzed using logistic regression analysis. Receiver operating characteristic (ROC) curves, areas under the curves (AUCs), and the Classification and Regression Tree (CART) algorithm were used to analyze treatment planning parameters as possible predictors for DQA failure. RESULTS: The AUC for leaf open time (LOT) was 0.70, and its cut-off point was approximately 30%. The ROC curve for the predicted probability calculated when the multivariate variable model was applied showed an AUC of 0.815. We confirmed that total monitor units, total dose, and LOT were significant predictors for DQA failure using the CART. CONCLUSIONS: The probability of DQA failure was higher when the percentage of LOT below 100 ms was higher than 30%. The percentage of LOT below 100 ms should be considered in the treatment planning process. The findings from this study may assist in the prediction of DQA failure in the future.

St. John's Wort Suppresses Growth in Triple-Negative Breast Cancer Cell Line MDA-MB-231 by Inducing Prodeath Autophagy and Apoptosis.

The rational regulation of programmed cell death by means of autophagy and apoptosis has been considered a potential treatment strategy for cancer. We demonstrated the inhibitory effect of St. John's Wort (SJW) on growth in the triple-negative breast cancer (TNBC) cell line and xenografted mice and its target mechanism concerning autophagic and apoptotic cell death. SJW ethanol extract (SJWE) inhibited proliferation in a dose-dependent manner. SJWE treatment dramatically increased autophagy flux and apoptosis compared with the control. The autophagy inhibitor, 3-methyladenine (3-MA), reversed the SJWE-induced inhibition of cell proliferation and regulation of autophagy and apoptosis, indicating that SJWE induced apoptosis through prodeath autophagy. Furthermore, SJWE inhibited tumor growth and induced autophagy and apoptosis in the tumor of MDA-MB-231 xenografted athymic nude mice. Our results indicate that SJWE might have great potential as a new anticancer therapy for triple-negative breast cancer by inducing prodeath autophagy and apoptosis.

Influence of Postoperative Finasteride Therapy on Recurrence of Gynecomastia After Mastectomy in Men Taking Finasteride for Alopecia.

Finasteride is commonly used for treatment of alopecia. Because finasteride is a cause of gynecomastia, there is concern regarding the continuation of finasteride therapy after mastectomy. No studies have been performed to determine whether finasteride should be continued after mastectomy when gynecomastia occurs in patients taking finasteride for the treatment of alopecia. The researchers studied the effects of finasteride on gynecomastia recurrence after mastectomy in men with gynecomastia taking finasteride for alopecia. The researchers retrospectively evaluated 1,673 patients with gynecomastia who underwent subcutaneous mastectomy with liposuction at Damsoyu Hospital from January 2014 to December 2016. In total, 52 of the patients were taking finasteride for alopecia before surgery and continued to use it in the same manner after mastectomy. Ultrasonography was performed 1 year after mastectomy. The patients' median age was 26.5 (24.75-30) years. All 52 patients had bilateral gynecomastia. The median duration of finasteride therapy before and after surgery was 12 (5-25.75) and 33 (27.5-40.5) months, respectively. There were no statistically significant differences between the groups with and without the use of finasteride in relation to postoperative complications and recurrence rates. Taking finasteride seems to have little effect on recurrence in patients with alopecia who have undergone surgical treatment of gynecomastia. Surgeons may recommend continuous finasteride therapy in patients with alopecia who wish to take finasteride after mastectomy.

Red pepper seed water extract inhibits preadipocyte differentiation and induces mature adipocyte apoptosis in 3T3-L1 cells.

BACKGROUND/OBJECTIVES: Reducing the number of adipocytes by inducing apoptosis of mature adipocytes as well as suppressing differentiation of preadipocytes plays an important role in preventing obesity. This study examines the anti-adipogenic and pro-apoptotic effect of red pepper seed water extract (RPS) prepared at 4℃ (RPS4) in 3T3-L1 cells. MATERIALS/METHODS: Effect of RPS4 or its fractions on lipid accumulation was determined in 3T3-L1 cells using oil red O (ORO) staining. The expressions of AMP-activated protein kinase (AMPK) and adipogenic associated proteins [peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding proteins α (C/EBP α), sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC)] were measured in 3T3-L1 cells treated with RPS4. Apoptosis and the expression of Akt and Bcl-2 family proteins [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad), Bcl-2 like protein 4 (Bax), Bal-2 homologous antagonist/killer (Bak)] were measured in mature 3T3-L1 cells treated with RPS4. RESULTS: Treatment of RPS4 (0-75 µg/mL) or its fractions (0-50 µg/mL) for 24 h did not have an apparent cytotoxicity on pre and mature 3T3-L1 cells. RPS4 significantly suppressed differentiation and cellular lipid accumulation by increasing the phosphorylation of AMPK and reducing the expression of PPAR-γ, C/EBP α, SREBP-1c, FAS, and ACC. In addition, all fractions except ethyl acetate fraction significantly suppressed cellular lipid accumulation. RPS4 induced the apoptosis of mature adipocytes by hypophosphorylating Akt, increasing the expression of the pro-apoptotic proteins, Bak, Bax, and Bad, and reducing the expression of the anti-apoptotic proteins, Bcl-2 and p-Bad. CONCLUSIONS: These finding suggest that RPS4 can reduce the numbers as well as the size of adipocytes and might useful for preventing and treating obesity.

Clinical Presentation and Outcomes of Middle East Respiratory Syndrome in the Republic of Korea.

BACKGROUND: From May to July 2015, the Republic of Korea experienced the largest outbreak of Middle East respiratory syndrome (MERS) outside the Arabian Peninsula. A total of 186 patients, including 36 deaths, had been diagnosed with MERS-coronavirus (MERS-CoV) infection as of September 30th, 2015. MATERIALS AND METHODS: We obtained information of patients who were confirmed to have MERS-CoV infection. MERS-CoV infection was diagnosed using real-time reverse-transcriptase polymerase chain reaction assay. RESULTS: The median age of the patients was 55 years (range, 16 to 86). A total of 55.4% of the patients had one or more coexisting medical conditions. The most common symptom was fever (95.2%). At admission, leukopenia (42.6%), thrombocytopenia (46.6%), and elevation of aspartate aminotransferase (42.7%) were observed. Pneumonia was detected in 68.3% of patients at admission and developed in 80.8% during the disease course. Antiviral agents were used for 74.7% of patients. Mechanical ventilation, extracorporeal membrane oxygenation, and convalescent serum were employed for 24.5%, 7.1%, and 3.8% of patients, respectively. Older age, presence of coexisting medical conditions including diabetes or chronic lung disease, presence of dyspnea, hypotension, and leukocytosis at admission, and the use of mechanical ventilation were revealed to be independent predictors of death. CONCLUSION: The clinical features of MERS-CoV infection in the Republic of Korea were similar to those of previous outbreaks in the Middle East. However, the overall mortality rate (20.4%) was lower than that in previous reports. Enhanced surveillance and active management of patients during the outbreak may have resulted in improved outcomes.

Anti-Diabetic Activities of Gastrodia elata Blume Water Extracts Are Mediated Mainly by Potentiating Glucose-Stimulated Insulin Secretion and Increasing ß-Cell Mass in Non-Obese Type 2 Diabetic Animals.

The brain is an important modulator of glucose metabolism, and is known to respond Gastrodia elata Blume water extract (GEB). Therefore, we examined whether long-term administration of GEB has hypoglycemic activity, and its action mechanism was explored in partially-pancreatectomized rats that exhibit similar characteristics as Asian type 2 diabetes, non-obese insulin-insufficient diabetes. The rats were provided high-fat diets supplemented with either of (1) 0.5% GEB (GEB-L), (2) 2% GEB (GEB-H), (3) 2% dextrin (control), or (4) 2% dextrin with rosiglitazone (20 mg/kg body weight; positive-control) for eight weeks. GEB dose-dependently improved hypothalamic insulin signaling, enhanced whole-body insulin sensitivity during hyperinsulinemic euglycemic clamp, and reduced hepatic glucose output in a hyperinsulinemic state. GEB dose-dependently increased the area under the curve of the serum insulin levels at the first and second phases during hyperglycemic clamp compared to the control, whereas the positive control had no effect. Insulin sensitivity during the hyperglycemic state also improved, dose-dependently, in response to GEB compared with that of the control, but was less than the positive control. GEB-H increased the mass of ß-cells by potentiating proliferation and decreasing apoptosis. In conclusion, GEB could be a therapeutic agent for treating Asian type 2 diabetes.

Intracranial hypertension as the first manifestation of primary Sjogren's syndrome.

BACKGROUND: Central nervous system involvement with primary Sjögren's syndrome (pSS) is rare, and often undiagnosed. Sjögren's syndrome and concomitant intracranial hypertension is a very rare event. CASE: We describe a patient with pSS who presented with intracranial hypertension as the initial symptom of the disease. CONCLUSION: This is the first case report of a patient with pSS that presented with intracranial hypertension only.

Cytotoxic Effects on HL-60 Cells of Myosin Light Chain Kinase Inhibitor ML-7 Alone and in Combination with Flavonoids.

Uncontrolled cell growth and increased cell proliferation are major features of cancer that are dependent on the stable structure and dynamics of the cytoskeleton. Since stable cytoskeleton structure and dynamics are partly regulated by myosin light chain kinase (MLCK), many current studies focused on MLCK inhibition as a chemotherapeutic target. As a potent and selective MLCK inhibitor, ML-7 [1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazapine hydrochloride] is a promising candidate for an anticancer agent, which would induce apoptosis as well as prevents invasion and metastasis in certain types of cancer cells. This study assessed cytotoxic effects of ML-7 against HL-60 cells and therapeutic efficacy of ML-7 as a potential antileukemia agent. Trypan-blue exclusion assays showed dose- and time- dependent decreases in ML-7 treated HL-60 cells (p < 0.05). Comet assays revealed a significant increase in DNA damage in HL-60 cells after treatment with 40 µM ML-7 for 2 h. Sub-G1 fractions, analyzed by flow cytometry increased in a dose-dependent manner, suggesting that ML-7 can induce apoptotic cell death in HL-60 cells. ML-7 was selectively cytotoxic towards HL-60 cells; not affecting normal human lymphocytes. That selective effect makes it a promising potential anti-leukemia agent. In addition, anticancer efficacy of ML-7 in combination with flavonoids (genistein or quercetin) or anticancer drugs (cisplatin or AraC) against HL-60 cells was assessed. Combination of ML-7 with flavonoids increased the anticancer effect of ML-7 to a greater extent than combination with the anticancer drugs. This implies that ML-7 in combination with flavonoids could increase the efficacy of anticancer treatment, while avoiding side effects cansed by conventional anticancer drug-containing combination chemotherapy.

A human case of gallbladder fascioliasis in Korea.

The authors would record the fifth case of human fascioliasis in Korea, occurring in a 48 year old Korean man who lived in Munkyong, Kyongsangbuk-do. The diagnosis was based on the morphology and measurements of the eggs which were collected in necrotic debris from the tunnel-like ulcerations of the gallbladder wall which was surgically removed for a gall stone. Although we failed to find out the fluke in the specimen, there found an evidence of once presence of Fasciola in the inflamed wall of the gallbladder in this patient.