Therapeutic effect of Nepenthes kampotiana Lecomte ethanol extract (Nk-EE) on androgenic alopecia through the inhibition of apoptosis and 5α-reductase activity.

There is increasing interest in hair loss treatment because a growing number of people affected. Nepenthes kampotiana Lecomte is known for its anticancer effects, but its potential for preventing hair loss has not been researched. Therefore, this study focused on the hair loss prevention effects of N. kampotiana Lecomte ethanol extract (Nk-EE). The results showed that Nk-EE had a proliferative effect on human follicle dermal papilla cells and inhibited cell death. In vivo experiments using androgenic areata models showed that Nk-EE had a positive effect on a variety of biomarkers such as hair-to-skin ratio, hair type frequency, and hair thickness. The results of this study suggest that Nk-EE has potential as an effective treatment for androgenic alopecia.

Long-Term Clinical Impact of Patients with Multi-Vessel Non-Obstructive Coronary Artery Disease.

BACKGROUND: Non-obstructive coronary artery disease (CAD) is a disease commonly diagnosed in patients undergoing coronary angiography. However, little is known regarding the long-term clinical impact of multi-vessel non-obstructive CAD. Therefore, the object of this study was to investigate the long-term clinical impact of multi-vessel non-obstructive CAD. METHOD: A total of 2083 patients without revascularization history and obstructive CAD were enrolled between January 2010 and December 2015. They were classified into four groups according to number of vessels involved in non-obstructive CAD (25% ≤ luminal stenosis < 70%): zero, one, two, or three diseased vessels (DVs). We monitored the patients for 5 years. The primary outcome was major cardiovascular and cerebrovascular events (MACCEs), defined as a composite of cardiac death, stroke, and myocardial infarction (MI). RESULT: The occurrence of MACCEs increased as the number of non-obstructive DVs increased, and was especially high in patients with three DVs. After adjustment, patients with three DVs still showed significantly poorer clinical outcomes of MACCEs, stroke, and MI compared those with zero DVs. CONCLUSION: Multi-vessel non-obstructive CAD, especially in patients with non-obstructive three DVs, is strongly associated with poor long-term clinical outcomes. This finding suggests that more intensive treatment may be required in this subset of patients.

Comparative Analysis of High-Intensity versus Low-to-Moderate Intensity Statin Therapy in Patients Undergoing Rotational Atherectomy for Calcified Coronary Artery Disease.

(1) Background: Moderate-intensity statin therapy, when compared to high-intensity statin therapy in Asian populations, has shown no significant difference in cardiovascular prognosis in small studies. The aim of this study was to compare the prognosis of patients based on statin intensity following rotational atherectomy (RA) during high-complexity percutaneous coronary intervention (PCI). (2) Methods: The ROCK registry, a multicenter retrospective study, included patients who had undergone rotational atherectomy (RA) during percutaneous coronary intervention (PCI) at nine tertiary medical centers in South Korea between January 2010 and October 2019. The patients were divided into high-intensity statin (H-statin) and moderate/low-intensity statin (M/L-statin) therapy groups. The primary endpoint includes outcomes (cardiac death, target vessel myocardial infarction (MI), and target vessel revascularization (TVR)) within an 18-month follow-up period. (3) Results: In this registry, a total of 540 patients with 583 lesions were included. We excluded 39 lesions from the analysis due to the absence of statin usage. The H-statin group had 394 lesions and the M/L-statin group had 150 lesions. There were no significant differences in baseline characteristics, procedural adverse events without heart failure history, triglycerides, or medications between the two groups. The procedural success rate showed a significant difference between the two groups. Multivariate analysis did not show a significant association between M/L-statin therapy and an increased risk of the primary endpoint. In propensity score matching analysis, no significant difference was observed in the primary endpoint either. (4) Conclusions: In high-complex RA PCI, moderate/low-intensity statin therapy is not inferior to high-intensity statin therapy in Korea.

Prognostic Impact of Atrial Fibrillation in Patients with Heavily Calcified Coronary Artery Disease Receiving Rotational Atherectomy.

Background and Objectives: Although both rotational atherectomy (RA) and atrial fibrillation (AF) have a high thrombotic risk, there have been no previous studies on the prognostic impact of AF in patients who undergo percutaneous coronary intervention (PCI) using RA. Thus, the aim of the present study was to determine the prognostic impact of AF in patients undergoing PCI using RA. Materials and Methods: A total of 540 patients who received PCI using RA were enrolled between January 2010 and October 2019. Patients were divided into AF and sinus rhythm groups according to the presence of AF. The primary endpoint was net adverse clinical events (NACEs) defined as a composite outcome of all-cause death, myocardial infarction, target vessel revascularization, cerebrovascular accident, or total bleeding. Results: Although in-hospital adverse events showed no difference between those with AF and those without AF (in-hospital events, 54 (11.0%) vs. 6 (12.2%), p = 0.791), AF was strongly associated with an increased risk of NACE at 3 years (NACE: hazard ratio, 1.880; 95% confidence interval, 1.096-3.227; p = 0.022). Conclusions: AF in patients who underwent PCI using RA was strongly associated with poor clinical outcomes. Thus, more attention should be paid to thrombotic and bleeding risks.

Anti-Inflammatory Effect of Meriania hexamera Sprague by Targeting Syk Kinase in NF-κB Signaling.

Inflammation is a protective mechanism against harmful stimuli. There are two types of inflammation, acute and chronic, and severe diseases such as cardiovascular disease and cancer can be caused by chronic inflammation. Therefore, this research was conducted to discover new anti-inflammatory drugs. Meriania hexamera Sprague is a common herb in the Amazon region in South America. It is used as a traditional medical herb by natives, but no studies to date have investigated its anti-inflammatory activity. Using lipopolysaccharide (LPS), pam3CSK4 (Pam3), and poly(I:C), we studied the M. hexamera Sprague-Methanol Extract's (Mh-ME) in vitro anti-inflammatory functions. Using RAW264.7 cells, we detected the released nitric oxide (NO) and mRNA expression extent of inducible nitric oxide synthase (iNOS) with pro-inflammatory proteins like tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and iterleukin-1 beta (IL-1ß). It was found that Mh-ME suppressed the inflammatory activities in a dose-dependent manner. In the luciferase assay, the nuclear factor kappa light chain enhancer of the activated B cells (NF-κB) pathway was inhibited by Mh-ME. Mh-ME especially acted as an inhibitor of Syk kinase according to the results from CETSA. We also confirmed that Mh-ME mitigates acute gastritis derived from HCl/EtOH in ICR mice, ameliorating the expression of IL-1ß and tumor necrosis factor-alpha (TNF-α). In conclusion, Mh-ME is an herb with anti-inflammatory effects that targets Syk in the NF-κB pathway, suggesting that Mh-ME could be used as an anti-inflammatory herbal medicine.

Extracellular production of a thermostable Cellvibrio endolytic ß-agarase in Escherichia coli for agarose liquefaction.

Four GH16 family ß-agarases (GH16A, GH16B, GH16C, and GH16D), originated from an agarolytic bacterium Cellvibrio sp. KY-GH-1, were expressed in an Escherichia coli system and their activities were compared. Only GH16B (597 amino acids, 63.8 kDa), with N-terminal 22-amino acid signal sequence, was secreted into the culture supernatant and demonstrated a robust endolytic agarose hydrolyzing activity for producing neoagarotetraose (NA4) and neoagarohexaose (NA6) as end products. The optimal temperature and pH for the enzyme activity were 50 °C and 7.0, respectively. The enzyme was stable up to 50 °C and over a pH range of 5.0-8.0. The kinetic parameters, including Km, Vmax, kcat, and kcat/Km, of GH16B ß-agarases for agarose were 14.40 mg/mL, 542.0 U/mg, 576.3 s-1, and 4.80 × 106 s-1 M-1, respectively. The addition of 1 mM MnCl2 and 15 mM tris(2-carboxyethyl)phosphine enhanced the enzymatic activity. When agarose or neoagaro-oligosaccharides were used as substrates, the end products of enzymatic catalysis were NA4 and NA6, whereas agaropentaose was produced along with NA4 and NA6 when agaro-oligosaccharides were used as substrates. Treatment of 9%[w/v] melted agarose with the enzyme (1.6 µg/mL) under continuous magnetic stirring at 50 °C for 14 h resulted in efficient agarose liquefaction into NA4 and NA6. Purification of NA4 and NA6 from the enzymatic hydrolysate (9%[w/v] agarose, 20 mL) via Sephadex G-15 column chromatography yielded ~ 650 mg NA4/~ 900 mg NA6 (i.e., ~ 85.3% of the theoretical maximum yield). These findings suggest that the recombinant thermostable GH16B ß-agarase is useful for agarose liquefaction to produce NA4 and NA6.

Ginsenosides from Panax ginseng as Key Modulators of NF-κB Signaling Are Powerful Anti-Inflammatory and Anticancer Agents.

Nuclear factor kappa B (NF-κB) signaling pathways progress inflammation and immune cell differentiation in the host immune response; however, the uncontrollable stimulation of NF-κB signaling is responsible for several inflammatory illnesses regardless of whether the conditions are acute or chronic. Innate immune cells, such as macrophages, microglia, and Kupffer cells, secrete pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1ß, via the activation of NF-κB subunits, which may lead to the damage of normal cells, including neurons, cardiomyocytes, hepatocytes, and alveolar cells. This results in the occurrence of neurodegenerative disorders, cardiac infarction, or liver injury, which may eventually lead to systemic inflammation or cancer. Recently, ginsenosides from Panax ginseng, a historical herbal plant used in East Asia, have been used as possible options for curing inflammatory diseases. All of the ginsenosides tested target different steps of the NF-κB signaling pathway, ameliorating the symptoms of severe illnesses. Moreover, ginsenosides inhibit the NF-κB-mediated activation of cancer metastasis and immune resistance, significantly attenuating the expression of MMPs, Snail, Slug, TWIST1, and PD-L1. This review introduces current studies on the therapeutic efficacy of ginsenosides in alleviating NF-κB responses and emphasizes the critical role of ginsenosides in severe inflammatory diseases as well as cancers.

Surgical Excision for Refractory Ischiogluteal Bursitis: A Consecutive Case Series of 21 Patients.

Purpose: A response to conservative treatment is usually obtained in cases of ischiogluteal bursitis. However, the time required to achieve relief of symptoms can vary from days to weeks, and there is a high recurrence rate, thus invasive treatment in addition to conservative treatment can occasionally be effective. Therefore, the aim of this study was to examine surgical excision in cases of refractory ischiogluteal bursitis and to evaluate patients' progression and outcome. Materials and Methods: A review of 21 patients who underwent surgical excision for treatment of ischiogluteal bursitis between February 2009 and July 2020 was conducted. Of these patients, seven patients were male, and 14 patients were female. Injection of steroid and local anesthetic into the ischial bursa was administered at outpatient clinics in all patients, who and they were refractory to conservative treatment, including aspiration and prescription drugs. Therefore, surgery was considered necessary. Excisions were performed by two orthopedic specialists using a direct vertical incision on the ischial area. A review of each patient was performed after excision, and quantification of the outcomes recorded using clinical scoring systems was performed. Results: The results of radiologic evaluation showed that the mean lesion size was 6.2 cm×4.5 cm×3.6 cm. The average disease course after excision was 21.6 days (range, 15-48 days). Measurement of clinical scores, including the visual analog scale and Harris hip scores, was performed during periodic visits, with scores of 0.7 (range, 0-2) and 98.1 (range, 96-100) at one postoperative month, respectively. Conclusion: Surgical excision, with an expectation of favorable results, could be considered for treatment of ischiogluteal bursitis that is refractory to therapeutic injections, aspirations, and medical prescriptions, particularly in moderate-to-severe cases.

The Preventive Effect of Specific Collagen Peptides against Dexamethasone-Induced Muscle Atrophy in Mice.

Muscle atrophy, also known as muscle wasting, is the thinning of muscle mass due to muscle disuse, aging, or diseases such as cancer or neurological problems. Muscle atrophy is closely related to the quality of life and has high morbidity and mortality. However, therapeutic options for muscle atrophy are limited, so studies to develop therapeutic agents for muscle loss are always required. For this study, we investigated how orally administered specific collagen peptides (CP) affect muscle atrophy and elucidated its molecular mechanism using an in vivo model. We treated mice with dexamethasone (DEX) to induce a muscular atrophy phenotype and then administered CP (0.25 and 0.5 g/kg) for four weeks. In a microcomputed tomography analysis, CP (0.5 g/kg) intake significantly increased the volume of calf muscles in mice with DEX-induced muscle atrophy. In addition, the administration of CP (0.25 and 0.5 g/kg) restored the weight of the gluteus maximus and the fiber cross-sectional area (CSA) of the pectoralis major and calf muscles, which were reduced by DEX. CP significantly inhibited the mRNA expression of myostatin and the phosphorylation of Smad2, but it did not affect TGF-ß, BDNF, or FNDC5 gene expression. In addition, AKT/mTOR, a central pathway for muscle protein synthesis and related to myostatin signaling, was enhanced in the groups that were administered CP. Finally, CP decreased serum albumin levels and increased TNF-α gene expression. Collectively, our in vivo results demonstrate that CP can alleviate muscle wasting through a multitude of mechanisms. Therefore, we propose CP as a supplement or treatment to prevent muscle atrophy.

Antioxidant, Anti-Inflammatory, Anti-Menopausal, and Anti-Cancer Effects of Lignans and Their Metabolites.

Since chronic inflammation can be seen in severe, long-lasting diseases such as cancer, there is a high demand for effective methods to modulate inflammatory responses. Among many therapeutic candidates, lignans, absorbed from various plant sources, represent a type of phytoestrogen classified into secoisolariciresionol (Seco), pinoresinol (Pino), matairesinol (Mat), medioresinol (Med), sesamin (Ses), syringaresinol (Syr), and lariciresinol (Lari). Lignans consumed by humans can be further modified into END or ENL by the activities of gut microbiota. Lignans are known to exert antioxidant and anti-inflammatory activities, together with activity in estrogen receptor-dependent pathways. Lignans may have therapeutic potential for postmenopausal symptoms, including cardiovascular disease, osteoporosis, and psychological disorders. Moreover, the antitumor efficacy of lignans has been demonstrated in various cancer cell lines, including hormone-dependent breast cancer and prostate cancer, as well as colorectal cancer. Interestingly, the molecular mechanisms of lignans in these diseases involve the inhibition of inflammatory signals, including the nuclear factor (NF)-κB pathway. Therefore, we summarize the recent in vitro and in vivo studies evaluating the biological effects of various lignans, focusing on their values as effective anti-inflammatory agents.

Clinical Outcomes of Biodegradable versus Durable Polymer Drug Eluting Stents in Rotational Atherectomy: Results from ROCK Registry.

BACKGROUND: The aim of this study was to compare the clinical outcomes of biodegradable polymer (BP) versus durable polymer (DP) drug eluting stents (DES) in patients with calcified coronary lesions who underwent rotational atherectomy (RA) and percutaneous coronary intervention (PCI). METHODS: This study was based on a multicenter registry which enrolled patients with calcified coronary artery disease who received PCI using RA during between January 2010 and October 2019 from 9 tertiary centers in Korea. The primary outcome was 3-year all-cause mortality, and the secondary outcomes were cardiovascular death and target-lesion failure. RESULTS: A total of 540 patients who underwent PCI using RA were enrolled with a follow-up period of median 16.1 months. From this registry, 272 patients with PCI using DP-DES and 238 patients with BP-SGDES were selected for analysis. PCI with BP-DES was associated with decreased all-cause mortality after propensity score matching (HR 0.414, CI 0.174-0.988) and multivariate Cox regression analysis (HR 0.458, HR 0.224-0.940). BP-DES was also associated with decreased cardiovascular mortality, but there was no difference in TLF between the two groups. CONCLUSIONS: BP-DES were associated with favorable outcomes compared to DP-DES in patients undergoing PCI using RA for calcified coronary lesions.

Impact of diabetes mellitus on periprocedural and 18-month clinical outcomes in Korean patients requiring rotational atherectomy: results from the ROCK Registry.

BACKGROUND: Diabetes mellitus (diabetes) increases the risk of severe coronary artery calcification, which increases the complexity of percutaneous coronary intervention requiring rotational atherectomy (RA) by interfering with lesion preparation, and limiting final stent expansion. OBJECTIVE: Investigate 30-day and 18-month clinical outcomes in patients with and without diabetes treated with percutaneous coronary intervention requiring RA. DESIGN: Medical record review SETTING: Multicenter registry in South Korea PATIENTS AND METHODS: The ROtational atherectomy in Calcified lesions in Korea (ROCK) registry was a large, retrospective, multicenter study to assess RA treatment of severe coronary artery calcification. MAIN OUTCOME MEASURES: The primary endpoint was target-vessel failure including cardiac death, target-vessel myocardial infarction, and target-vessel revascularization. SAMPLE SIZE: 540 patients followed for a median of 16.1 months. RESULTS: Of the 540 patients, 305 had diabetes (56.5%). The diabetes group had a significantly higher frequency of multivessel disease; comorbidities such as hypertension, dyslipidemia, and chronic kidney disease; and lower ejection fraction of the left ventricle compared to the non-diabetes group (n=235). There were no significant differences in procedure success and complications observed between the two groups. Target vessel failure at 30 days between the diabetes and non-diabetes groups was not statistically significant in a multivariate Cox regression analysis (1.6% vs. 2.6%, adjusted hazard ratio [HR] 0.595, 95% confidence interval [CI] 0.154-2.300, P=.451). During an 18-month follow-up, the risk of target vessel failure was higher (12.5% vs. 8.9%) but the difference was not statistically significant (adjusted HR 1.393, 95% CI 0.782-2.482, P=.260). CONCLUSIONS: Patients with diabetes have a risk of complications comparable to patients without diabetes, and 30-day and 18-month clinical outcomes are similar in severe coronary artery calcification requiring RA, despite having more comorbidities. LIMITATIONS: Retrospective design. Sample size not based on power calculation. CONFLICT OF INTEREST: None.

Impact of Diabetes Duration on Clinical Outcome in Patients Receiving Rotational Atherectomy in Calcified Lesions in Korea-Results from ROCK Registry.

There are limited data regarding the clinical impact of diabetes duration for patients with heavy calcified coronary lesions. We sought to determine the clinical impact of diabetes duration on clinical outcomes in patients with heavily calcified lesions who required rotational atherectomy during percutaneous coronary intervention (PCI). A total of 540 diabetic patients (583 lesions) were enrolled between January 2010 and October 2019. Patients were classified into three subgroups: patients with no diabetes mellitus (non-DM), shorter duration (S-DM), and longer duration (L-DM), of which duration was divided at 10 years. During 18 months of follow-up-duration, diabetes duration was significantly associated with the primary outcome. The incidence rate of target-vessel failure (TVF), the primary outcome, was significantly higher in the L-DM group compared with non-DM or S-DM. Among secondary outcomes, any repeat revascularization (RR) was frequently observed in the L-DM compared with other groups. In multivariate analysis, the risk of TVF and any RR was 1.9 times and 2.4 times higher in L-DM than in non-DM, respectively. This study firstly demonstrated that there is an association between a longer DM duration and poor clinical outcomes in patients with severe calcified CAD after PCI. More careful monitoring for recurrence is needed during follow-up in those patients.

Connarus semidecandrus Jack Exerts Anti-Alopecia Effects by Targeting 5α-Reductase Activity and an Intrinsic Apoptotic Pathway.

There is a growing demand for hair loss treatments with minimal side effects and recurrence potential. Connarus semidecandrus Jack has been used as a folk medicine for fever in tropical regions, but its anti-alopecia effects remain unclear. In this study, the anti-androgenic alopecia effect of an ethanol extract of Connarus semidecandrus Jack (Cs-EE) was demonstrated in a testosterone-induced androgenic alopecia (AGA) model, in terms of the hair-skin ratio, hair type frequency, and hair thickness. The area of restored hair growth and thickened hair population after Cs-EE treatment showed the hair-growth-promoting effect of Cs-EE. Histological data support the possibility that Cs-EE could reduce hair loss and upregulate hair proliferation in mouse skin by shifting hair follicles from the catagen phase to the anagen phase. Western blotting indicated that Cs-EE reduced the expression of the androgenic receptor. Cs-EE treatment also inhibited programmed cell death by upregulating Bcl-2 expression at the mRNA and protein levels. The anti-alopecia effect of Cs-EE was confirmed by in vitro experiments showing that Cs-EE had suppressive effects on 5-α reductase activity and lymph node carcinoma of the prostate proliferation, and a proliferative effect on human hair-follicle dermal papilla (HDP) cells. Apoptotic pathways in HDP cells were downregulated by Cs-EE treatment. Thus, Cs-EE could be a potential treatment for AGA.

Novel BiVO4-nanosheet-supported MoS2-nanoflake-heterostructure with synergistic enhanced photocatalytic removal of tetracycline under visible light irradiation.

This paper describes a simple in-situ hydrothermal technique for the production of BiVO4/MoS2 binary nanocomposites as visible-light-driven catalysts. The as-prepared samples were analyzed by structural, morphological, compositional, optical, surface area, and photocurrent analyses. The lattice fringe spaces at 0.304 nm and 0.612 nm were indexed to the (112) and (002) crystal planes of BiVO4 and MoS2, respectively. Antibacterial photocatalytic capabilities were assessed using tetracycline (TC). Consequently, it was observed that the BiVO4/MoS2 nanocomposite demonstrated improved antibacterial removal ability compared with the pristine samples. The BiVO4/MoS2 nanocomposite exhibited 97.46% removal of TC compared with the pure BiVO4 (43.76%) and MoS2 (35.28%) samples within 90 min. Thus, the photocatalytic performance was observed to follow the given order: BiVO4/MoS2 nanocomposite > BiVO4 > MoS2. The removal of TC after 90 min of irradiation was approximately 97.46%, 96.62%, 95.59%, and 94.45% after the 1st, 2nd, 3rd, and 4th cycles, respectively. Thus, the recycling tests revealed the stability of the photocatalyst, which exhibited a TC removal efficiency of 94.45% without distinct decay, even after the 4th cycle. According to the trapping results, hydroxyl radicals and holes were the key species and demonstrated a greater influence on the photocatalytic performance than superoxide radicals. The increased activity of the BiVO4/MoS2 nanocomposite may be attributed to its large surface area and tunable bandgap, which accelerate the charge-transport characteristics of the photocatalytic system. This insight and synergetic effects can provide a new approach for the development of novel heterostructure photocatalysts.

Angiopteris cochinchinensis de Vriese Ameliorates LPS-Induced Acute Lung Injury via Src Inhibition.

Growing demand for treatment options against acute lung injury (ALI) emphasizes studies on plant extracts harboring anti-inflammatory effects. According to GC-MS analysis, Angiopteris cochinchinensis de Vriese consists of various flavonoids with anti-inflammatory activities. Thus, in this study, the anti-inflammatory effects of an extract of Angiopteris cochinchinensis de Vriese (Ac-EE) were assessed using RAW264.6 murine macrophages and a lipopolysaccharide (LPS)-induced ALI model. Ac-EE reduced the nitric oxide production in murine macrophages increased by LPS induction. Moreover, protective effects of Ac-EE on lung tissue were demonstrated by shrinkage of edema and lung injury. Reduced neutrophil infiltration and formation of hyaline membranes were also detected in lung tissues after H&E staining. Semiquantitative RT-PCR, quantitative real-time PCR, and ELISA showed that Ac-EE inhibits the production of proinflammatory mediators, including iNOS and COX-2, and cytokines, such as TNF-α, IL-1ß, and IL-6. An Ac-EE-mediated anti-inflammatory response was derived from inhibiting the NF-κB signaling pathway, which was evaluated by luciferase reporter assay and Western blotting analysis. A cellular thermal shift assay revealed that the prime target of Ac-EE in alleviating inflammation was Src. With its direct binding with Src, Angiopteris cochinchinensis de Vriese significantly mitigates lung injury, showing possibilities of its potential as an effective botanical drug.

Anti-Melanogenesis Effects of a Cyclic Peptide Derived from Flaxseed via Inhibition of CREB Pathway.

Linosorbs (Los) are cyclic peptides from flaxseed oil composed of the LO mixture (LOMIX). The activity of LO has been reported as being anti-cancer and anti-inflammatory. However, the study of skin protection has still not proceeded. In particular, there are poorly understood mechanisms of melanogenesis to LO. Therefore, we investigated the anti-melanogenesis effects of LOMIX and LO, and its activity was examined in mouse melanoma cell lines. The treatment of LOMIX (50 and 100 µg/mL) and LO (6.25-50 µM) suppressed melanin secretion and synthesis, which were 3-fold increased, in a dose-dependent manner, up to 95%. In particular, [1-9-NαC]-linusorb B3 (LO1) and [1-9-NαC]-linusorb B2 (LO2) treatment (12.5 and 25 µM) highly suppressed the synthesis of melanin in B16F10 cell lines up to 90%, without toxicity. LOMIX and LOs decreased the 2- or 3-fold increased mRNA levels, including the microphthalmia-associated transcription factor (MITF), Tyrosinase, tyrosinase-related protein 1 (TYRP1), and tyrosinase-related protein 2 (TYRP2) at the highest concentration (25 µM). Moreover, the treatment of 25 µM LO1 and LO2 inhibited the expression of MITF and phosphorylation of upper regulatory proteins such as CREB and PKA. Taken together, these results suggested that LOMIX and its individual LO could inhibit melanin synthesis via downregulating the CREB-dependent signaling pathways, and it could be used for novel therapeutic materials in hyperpigmentation.

Expression profile of CD98 heavy chain and L-type amino acid transporter 1 and its prognostic significance in colorectal cancer.

L-type amino acid transporter (LAT1) is a neutral amino acid transporter, forming a heterodimer complex with the CD98 heavy chain (CD98hc). In this study, we studied the expression profiles of LAT1 and CD98hc in colorectal cancer (CRC) and its precursor lesions. Transcription levels of CD98hc and LAT1 were significantly increased in CRC compared to the matched normal mucosa. CD98hc and LAT1 expression showed no significant correlations with cancer stem cell markers and intestinal stem cell markers, whereas both had positive correlations with Wnt target genes, AXIN2, and EPHB2, suggesting an association with aberrant Wnt signaling activation. Immunohistochemical analysis revealed that CD98hc and LAT1 are not expressed in normal colonic mucosa and various benign lesions including hyperplastic polyps and sessile and traditional serrated adenomas. CD98hc and LAT1 expressions began to appear in tubular adenomas and further increased in carcinomas. Of interest, CD98hc expression decreased during lymph node metastasis. Survival analysis demonstrated that CD98hc and LAT1 have no significant prognostic effect in CRCs. In conclusion, CD98hc and LAT1 are not normally expressed in colonic mucosa and most benign lesions. Their expression began to appear in tubular adenomas and further increased during the adenoma-to-carcinoma transition. CD98hc expression decreased while metastasizing to regional lymph nodes. However, CD98hc and LAT1 expressions had no prognostic value in patients with CRC.

How Should Patients with a Thoracolumbar Injury Classification and Severity Score of 4 Be Treated?

The thoracolumbar injury classification and severity score (TLICS) system help surgeons decide whether patients should undergo initial operative treatment or nonoperative treatment. However, the best treatment for patients with TLICS 4 fracture remains unknown. The aim of this study was to identify the risk factors for nonoperative treatment failure in patients with TLICS 4 fracture and establish treatment standards for TLICS 4 fractures. This study included 44 patients with TLICS 4 fracture who initially received nonoperative treatment. We divided these patients into two groups: the successful nonoperative treatment group included 18 patients, and the operative treatment group after nonoperative treatment failure included 26 patients. In multiple logistic regression analysis, spinal canal compromise (odd ratio = 1.316) and kyphotic angle (odd ratio = 1.416) were associated with nonoperative treatment failure in patients with TLICS 4 fracture. Other factors, including age, sex, BMI, initial VAS score, and loss of vertebral body height, were not significantly associated with nonoperative treatment failure in these patients. Spinal canal compromise and kyphotic angle were associated with nonoperative treatment failure in patients with TLICS 4 fracture. Therefore, we recommend the surgeon observe spinal canal compromise and kyphotic angle more carefully when deciding on the treatment of patients with TLICS 4 fracture.

Effect of smoking on clinical outcomes in patients receiving rotational atherectomy in calcified coronary lesions: from the ROCK Registry, South Korea.

BACKGROUND: Tobacco smoking and its harmful health effects also increase economic burdens globally. Surprisingly, despite the detrimental health consequences of smoking, some studies have shown better survival among smokers compared with non-smokers, a phenomenon called "smoker's paradox". However, the impact of smoking status on clinical outcomes in severe calcified coronary artery disease (CAD) patients has yet to be reported. OBJECTIVES: Investigate the impact of smoking on clinical outcomes in calcified CAD receiving rotational atherectomy (RA). DESIGN: Retrospective review of medical records. SETTING: Multicenter registry in South Korea. PATIENTS AND METHODS: This multicenter registry included consecutive patients with calcified CAD who underwent RA at nine tertiary centers in Korea between January 2010 and October 2019. MAIN OUTCOME MEASURES: Target-vessel failure (TVF) which included the composite of cardiac death, target-vessel myocardial infarction (TVMI), and target-vessel revascularization (TVR). SAMPLE SIZE: 583 lesions in 540 patients followed for a median of 16.1 months. RESULTS: Lesions were divided into two groups: non-smokers (n=472, 81.0%) and smokers (n=111, 19.0%). TVF in the smoker group was significantly more frequent than in non-smoker group (log rank P=.016). The inverse probability of treatment weighting analysis also showed that smoking was significantly associated with a higher incidence of the primary outcome (HR: 1.617; 95% CI: 1.127-2.320; P=.009), cardiac death (HR 1.912; 95% CI: 1.105-3.311; P=.021), myocardial infarction (HR: 3.914; 95% CI: 1.884-8.132; P<.001), TVMI (HR: 3.234; 95% CI: 1.130-9.258; P=.029), and TVR (HR: 1.661; 95% CI: 1.043-2.643; P=.032). However, any bleeding was significantly observed less in the smokers. CONCLUSION: Smoking is significantly associated with adverse clinical outcomes in CAD patients requiring RA. LIMITATIONS: Retrospective design. CONFLICTS OF INTEREST: None.