Validation of Downloadable Mobile Snore Applications by Polysomnography (PSG).

Purpose: Obstructive sleep apnea (OSA) is a common breathing disorder during sleep that is associated with symptoms such as snoring, excessive daytime sleepiness, and breathing interruptions. Polysomnography (PSG) is the most reliable diagnostic test for OSA; however, its high cost and lengthy testing duration make it difficult to access for many patients. With the availability of free snore applications for home-monitoring, this study aimed to validate the top three ranked snore applications, namely SnoreLab (SL), Anti Snore Solution (ASS), and Sleep Cycle Alarm (SCA), using PSG. Patients and Methods: Sixty participants underwent an overnight PSG while simultaneously using three identical smartphones with the tested apps to gather sleep and snoring data. Results: The study discovered that all three applications were significantly correlated with the total recording time and snore counts of PSG, with ASS showing good agreement with snore counts. Furthermore, the Snore Score, Time Snoring of SL, and Sleep Quality of SCA had a significant correlation with the natural logarithm of apnea hypopnea index (lnAHI) of PSG. The Snore Score of SL and the Sleep Quality of SCA were shown to be useful for evaluating snore severity and for pre-diagnosing or predicting OSA above moderate levels. Conclusion: These findings suggest that some parameters of free snore applications can be employed to monitor OSA progress, and future research could involve adjusted algorithms and larger-scale studies to further authenticate these downloadable snore and sleep applications.

Engineered extracellular vesicles carrying let-7a-5p for alleviating inflammation in acute lung injury.

BACKGROUND: Acute lung injury (ALI) is a life-threatening respiratory condition characterized by severe inflammation and lung tissue damage, frequently causing rapid respiratory failure and long-term complications. The microRNA let-7a-5p is involved in the progression of lung injury, inflammation, and fibrosis by regulating immune cell activation and cytokine production. This study aims to use an innovative cellular electroporation platform to generate extracellular vesicles (EVs) carring let-7a-5p (EV-let-7a-5p) derived from transfected Wharton's jelly-mesenchymal stem cells (WJ-MSCs) as a potential gene therapy for ALI. METHODS: A cellular nanoporation (CNP) method was used to induce the production and release of EV-let-7a-5p from WJ-MSCs transfected with the relevant plasmid DNA. EV-let-7a-5p in the conditioned medium were isolated using a tangential flow filtration (TFF) system. EV characterization followed the minimal consensus guidelines outlined by the International Society for Extracellular Vesicles. We conducted a thorough set of therapeutic assessments, including the antifibrotic effects using a transforming growth factor beta (TGF-ß)-induced cell model, the modulation effects on macrophage polarization, and the influence of EV-let-7a-5p in a rat model of hyperoxia-induced ALI. RESULTS: The CNP platform significantly increased EV secretion from transfected WJ-MSCs, and the encapsulated let-7a-5p in engineered EVs was markedly higher than that in untreated WJ-MSCs. These EV-let-7a-5p did not influence cell proliferation and effectively mitigated the TGF-ß-induced fibrotic phenotype by downregulating SMAD2/3 phosphorylation in LL29 cells. Furthermore, EV-let-7a-5p regulated M2-like macrophage activation in an inflammatory microenvironment and significantly induced interleukin (IL)-10 secretion, demonstrating their modulatory effect on inflammation. Administering EVs from untreated WJ-MSCs slightly improved lung function and increased let-7a-5p expression in plasma in the hyperoxia-induced ALI rat model. In comparison, EV-let-7a-5p significantly reduced macrophage infiltration and collagen deposition while increasing IL-10 expression, causing a substantial improvement in lung function. CONCLUSION: This study reveals that the use of the CNP platform to stimulate and transfect WJ-MSCs could generate an abundance of let-7a-5p-enriched EVs, which underscores the therapeutic potential in countering inflammatory responses, fibrotic activation, and hyperoxia-induced lung injury. These results provide potential avenues for developing innovative therapeutic approaches for more effective interventions in ALI.

The effect of a helmet type, home-use low-level light therapy device for chemotherapy-induced alopecia: study protocol for a randomized controlled trial.

BACKGROUND: Alopecia is one of the most common adverse effects of chemotherapy. It reduces the patient's self-esteem and quality of life and the effect of therapy. Scalp cooling is the only verified current method for prevention but success is not guaranteed, particularly after receiving anthracycline-based combinations. Low-level light therapy has been clinically proven to inhibit the progress of androgenic alopecia. A previous study using human subjects shows limited benefits for low-level light therapy for patients who suffer chemotherapy-induced alopecia but an increase in the number of probes and the optimization of light sources may improve the efficacy. This study determines the efficacy of low-level light therapy for the prevention of chemotherapy-induced hair loss for patients with breast cancer using a randomized controlled trial. METHODS: One hundred six eligible breast cancer patients were randomly distributed into a low-level light therapy group and a control group, after receiving chemotherapy. Subjects in the low-level light therapy group received 12 courses of intervention within 4 weeks. Subjects in the control group received no intervention but were closely monitored. The primary outcome is measured as the difference in the hair count in a target area between the baseline and at the end of week 4, as measured using a phototrichogram (Sentra scalp analyzer). The secondary outcomes include the change in hair count at the end of week 1, week 2, and week 3 and hair width at the end of week 1, week 2, week 3, and week 4, as measured using a phototrichogram, and the change in distress, the quality of life, and self-esteem due to chemotherapy-induced alopecia, at the end of week 4, as measured using a questionnaire. DISCUSSION: This study improves cancer patients' quality of life and provides clinical evidence. TRIAL REGISTRATION: Registered at ClinicalTrials.gov- NCT05397457 on 1 June 2022.

An updated review of the immunological mechanisms of keloid scars.

Keloid is a type of disfiguring pathological scarring unique to human skin. The disorder is characterized by excessive collagen deposition. Immune cell infiltration is a hallmark of both normal and pathological tissue repair. However, the immunopathological mechanisms of keloid remain unclear. Recent studies have uncovered the pivotal role of both innate and adaptive immunity in modulating the aberrant behavior of keloid fibroblasts. Several novel therapeutics attempting to restore regulation of the immune microenvironment have shown variable efficacy. We review the current understanding of keloid immunopathogenesis and highlight the potential roles of immune pathway-specific therapeutics.

The efficacy and safety of traditional Chinese medicine Guilu Erxian Jiao in the treatment of knee osteoarthritis: A systematic review and meta-analysis.

OBJECTIVE: A systematic review was conducted to investigate the efficacy of Guilu Erxian Jiao (GEJ) in the treatment of knee osteoarthritis (OA). METHODS: We searched PubMed, MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese Electronic Periodical Services, and ClinicalTrials.gov to identify relevant randomized controlled trials or controlled clinical trials, from the inception of each source to April 20, 2021. Primary outcome included overall efficacy, pain score, and Lequesne index score; secondary outcome included adverse events. Methodological quality was assessed using the Cochrane risk of bias tool (RoB 1.0). The meta-analysis was performed based on a random-effects model due to anticipated clinical heterogeneity. The grading of overall evidence was assessed using the GRADE system. The study protocol was registered on PROSPERO (CRD42021233573). RESULTS: Eight studies were included. Compared to controls, GEJ exhibited superior overall efficacy for treating OA (risk ratio (RR) = 1.20; 95% confidence interval (CI) = 1.06-1.35). Regarding pain score, there was no statistical difference between GEJ and controls (standardized mean difference (SMD) = 0.27; 95% CI = -0.91 - 1.46). No significant difference was found in Lequesne score between GEJ and controls (MD = -0.25; 95% CI = -0.52 - 0.01). No statistical difference in adverse reactions was observed between GEJ and controls (risk difference (RD) = -0.01; 95% CI = -0.05-0.03). CONCLUSION: Our findings suggest that GEJ may have positive effects on overall efficacy in treating OA. However, there is insufficient evidence regarding pain score, Lequesne score, and knee joint function score.

Gamma-mangostin isolated from garcinia mangostana suppresses colon carcinogenesis and stemness by downregulating the GSK3ß/ß-catenin/CDK6 cancer stem pathway.

BACKGROUND: Despite advances in chemotherapies and targeted drugs, colorectal cancer (CRC) remains challenging to treat due to drug resistance. Emerging evidence indicates that cancer-associated fibroblasts (CAFs) facilitate the generation of cancer stem-like cells (CSCs) and drug resistance. Glycogen synthase kinase-3 (GSK) associated signaling pathways have been implicated in the generation of CSCs and represent a target for therapeutics development. HYPOTHESIS: Gamma-mangostin (gMG) isolated from Garcinia mangostana was evaluated for its ability to downregulate GSK3ß-associated signaling in CRC cells and overcome CAF-induced 5-fluorouracil resistance and CSC generation. METHODS: Bioinformatics analysis, in silico molecular docking, in vitro assays, including cell viability tests, colony- and tumor sphere-formation assays, transwell migration assays, ELISA, SDS-PAGE, Western blotting, miR expression, qPCR, and flow cytometry, as well as in vivo mouse xenograft models were used to evaluate the antitumor effects of gMG. RESULTS: Bioinformatics analyses indicated that GSK3ß/CDK6/ß-catenin mRNA signature was significantly higher in colon cancer patients. Additional algorithms predicted a higher miR-26b level was associated with significantly higher survival in CRC patients and GSK3ß and CDK6 as targets of miR-26b-5p. To validate these findings in vitro, we showed that CAF-cocultured CRC cells expressed an increased expression of GSK3ß, ß-catenin, CDK6, and NF-κB. Therapeutically, we demonstrated that gMG treatment suppressed GSK3ß-associated signaling pathways while concomitantly increased the miR-26b-5p level. Using a xenograft mouse model of CAFs cocultured HCT116 tumorspheres, we showed that gMG treatment reduced tumor growth and overcame CAF-induced 5-fluorouracil resistance. CONCLUSIONS: Pharmacological intervention with gMG suppressed CRC carcinogenesis and stemness via downregulating GSK3/ß-catenin/CDK6 and upregulating the miR-26b-5p tumor suppressor. Thus, gMG represents a potential new CRC therapeutic agent and warrants further investigation.

Identification of NSP3 (SH2D3C) as a Prognostic Biomarker of Tumor Progression and Immune Evasion for Lung Cancer and Evaluation of Organosulfur Compounds from Allium sativum L. as Therapeutic Candidates.

The multi-domain non-structural protein 3 (NSP3) is an oncogenic molecule that has been concomitantly implicated in the progression of coronavirus infection. However, its oncological role in lung cancer and whether it plays a role in modulating the tumor immune microenvironment is not properly understood. In the present in silico study, we demonstrated that NSP3 (SH2D3C) is associated with advanced stage and poor prognoses of lung cancer cohorts. Genetic alterations of NSP3 (SH2D3C) co-occurred inversely with Epidermal Growth Factor Receptor (EGFR) alterations and elicited its pathological role via modulation of various components of the immune and inflammatory pathways in lung cancer. Our correlation analysis suggested that NSP3 (SH2D3C) promotes tumor immune evasion via dysfunctional T-cell phenotypes and T-cell exclusion mechanisms in lung cancer patients. NSP3 (SH2D3C) demonstrated a high predictive value and association with therapy resistance in lung cancer, hence serving as an attractive target for therapy exploration. We evaluated the in silico drug-likeness and NSP3 (SH2D3C) target efficacy of six organosulfur small molecules from Allium sativum using a molecular docking study. We found that the six organosulfur compounds demonstrated selective cytotoxic potential against cancer cell lines and good predictions for ADMET properties, drug-likeness, and safety profile. E-ajoene, alliin, diallyl sulfide, 2-vinyl-4H-1,3-dithiin, allicin, and S-allyl-cysteine docked well into the NSP3 (SH2D3C)-binding cavity with binding affinities ranging from -4.3~-6.70 A and random forest (RF) scores ranging from 4.31~5.26 pKd. However, S-allyl-cysteine interaction with NSP3 (SH2D3C) is unfavorable and hence less susceptible to NSP3 ligandability. In conclusion, our study revealed that NSP3 is an important onco-immunological biomarker encompassing the tumor microenvironment, disease staging and prognosis in lung cancer and could serve as an attractive target for cancer therapy. The organosulfur compounds from A. sativum have molecular properties to efficiently interact with the binding site of NSP3 and are currently under vigorous preclinical study in our laboratory.

Positive Effects of Laser Acupuncture in Methamphetamine Users Undergoing Group Cognitive Behavioral Therapy: A Pilot Study.

BACKGROUND: Methamphetamine (MA) addiction has become a crucial public health concern because of its adverse consequences to individuals and the society. OBJECTIVE: To investigate the clinical efficacy of laser acupuncture combined with group cognitive behavioral therapy for MA addiction treatment. MATERIALS AND METHODS: MA users who participated in group cognitive behavioral therapy and met the inclusion criteria were referred from psychiatrists to participate. The participants received laser acupuncture treatment once a week for 2 months (total eight treatments) on selected acupoints (PC6, HT7, LI4, ST36, SP6, and LR3). Laboratory assessment included urinalysis for MA and liver function tests aspartate aminotransferase, alanine aminotransferase, and γ-glutamyltransferase (AST, ALT, and γ-GT), whereas the objective assessment included visual analog scale (VAS) for MA craving and refusal and Pittsburgh sleep quality index (PSQI), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI) questionnaires. All data were collected before and at 1 and 2 months after treatment. Cognitive behavioral therapy completion rate and rate of relapse to MA use were also determined. RESULT: Fifteen participants were enrolled, of whom seven completed the trial. Urinalysis for MA revealed a decrease in drug use from 57.1% to 28.6%. Compared with those before treatment, PSQI scores were significantly lower at 1 and 2 months after treatment (-3.73 and -4.10, respectively; both p < 0.001), and so were BDI scores (-5.64 and -8.17, respectively; p=0.01 and 0.001, respectively). However, no significant difference was observed in the liver function test, VAS of craving and refusal, and BAI results. A slight improvement in the motivation for drug abstinence and anxiety was observed during the treatment course. Participants reported no adverse events. CONCLUSION: Laser acupuncture combined with group cognitive behavioral therapy may improve sleep quality, alleviate depression, and reduce MA use. Additional large-scale studies confirming the effectiveness of this modality are warranted.

The Beneficial Effects of Moxibustion on Overweight Adolescent Girls.

Among adolescent girls, overweight or obesity has both physical and psychological involvement. We conducted a randomized controlled trial of moxibustion using a moxa burner. Fifty-four eligible girls aged 15-18 years with a body mass index (BMI) greater than 25.3 were enrolled in the study. The girls were randomly allocated to the treatment (n = 27) and control (n = 27) groups. The girls underwent treatment three times per week for 8 weeks (24 treatments). Moxibustion was applied to the RN12, RN6, ST25, ST36, and SP6 acupoints. Physical assessments were BMI, waist-to-hip ratio (WHR), and body fat ratio (BFR). Psychological outcomes were measured using the Rosenberg Self-Esteem Scale (RSE). Data were collected at the beginning of the study (baseline), week 4, and week 8. Of the 54 participants, 46 completed the trial. The difference in mean BMI from baseline between the two groups was 0.097 (p=0.655) at week 4 and -0.794 (p=0.001) at week 8. The mean WHR of the treatment group was significantly reduced compared with baseline, with a -0.011 (p=0.017) and -0.035 (p < 0.001) mean change at weeks 4 and 8, respectively. The mean BFR was slightly reduced (-0.253;p=0.474 ) at week 4 compared with baseline in the treatment group. At week 8, it was significantly reduced (-2.068; p < 0.001) from baseline in the treatment group. The mean RSE in the treatment group showed no significant increase from baseline at week 4 (0.155 points, p=0.803), but it improved significantly from baseline at week 8 (1.606 points, p=0.021) compared to that in the control group. No obvious adverse effect was reported during this study. Moxibustion using a moxa burner may be an effective and safe intervention for overweight adolescent girls, having both physical and psychological benefits.

Honeysuckle Aqueous Extracts Induced let-7a Suppress EV71 Replication and Pathogenesis In Vitro and In Vivo and Is Predicted to Inhibit SARS-CoV-2.

Honeysuckle (Lonicera japonica Thunb) is a traditional Chinese medicine (TCM) with an antipathogenic activity. MicroRNAs (miRNAs) are small non-coding RNA molecules that are ubiquitously expressed in cells. Endogenous miRNA may function as an innate response to block pathogen invasion. The miRNA expression profiles of both mice and humans after the ingestion of honeysuckle were obtained. Fifteen overexpressed miRNAs overlapped and were predicted to be capable of targeting three viruses: dengue virus (DENV), enterovirus 71 (EV71) and SARS-CoV-2. Among them, let-7a was examined to be capable of targeting the EV71 RNA genome by reporter assay and Western blotting. Moreover, honeysuckle-induced let-7a suppression of EV71 RNA and protein expression as well as viral replication were investigated both in vitro and in vivo. We demonstrated that let-7a targeted EV71 at the predicted sequences using luciferase reporter plasmids as well as two infectious replicons (pMP4-y-5 and pTOPO-4643). The suppression of EV71 replication and viral load was demonstrated in two cell lines by luciferase activity, RT-PCR, real-time PCR, Western blotting and plaque assay. Furthermore, EV71-infected suckling mice fed honeysuckle extract or inoculated with let-7a showed decreased clinical scores and a prolonged survival time accompanied with decreased viral RNA, protein expression and virus titer. The ingestion of honeysuckle attenuates EV71 replication and related pathogenesis partially through the upregulation of let-7a expression both in vitro and in vivo. Our previous report and the current findings imply that both honeysuckle and upregulated let-7a can execute a suppressive function against the replication of DENV and EV71. Taken together, this evidence indicates that honeysuckle can induce the expression of let-7a and that this miRNA as well as 11 other miRNAs have great potential to prevent and suppress EV71 replication.

Honeysuckle (Lonicera japonica) and Huangqi (Astragalus membranaceus) Suppress SARS-CoV-2 Entry and COVID-19 Related Cytokine Storm in Vitro.

COVID-19 is threatening human health worldwide but no effective treatment currently exists for this disease. Current therapeutic strategies focus on the inhibition of viral replication or using anti-inflammatory/immunomodulatory compounds to improve host immunity, but not both. Traditional Chinese medicine (TCM) compounds could be promising candidates due to their safety and minimal toxicity. In this study, we have developed a novel in silico bioinformatics workflow that integrates multiple databases to predict the use of honeysuckle (Lonicera japonica) and Huangqi (Astragalus membranaceus) as potential anti-SARS-CoV-2 agents. Using extracts from honeysuckle and Huangqi, these two herbs upregulated a group of microRNAs including let-7a, miR-148b, and miR-146a, which are critical to reduce the pathogenesis of SARS-CoV-2. Moreover, these herbs suppressed pro-inflammatory cytokines including IL-6 or TNF-α, which were both identified in the cytokine storm of acute respiratory distress syndrome, a major cause of COVID-19 death. Furthermore, both herbs partially inhibited the fusion of SARS-CoV-2 spike protein-transfected BHK-21 cells with the human lung cancer cell line Calu-3 that was expressing ACE2 receptors. These herbs inhibited SARS-CoV-2 Mpro activity, thereby alleviating viral entry as well as replication. In conclusion, our findings demonstrate that honeysuckle and Huangqi have the potential to be used as an inhibitor of SARS-CoV-2 virus entry that warrants further in vivo analysis and functional assessment of miRNAs to confirm their clinical importance. This fast-screening platform can also be applied to other drug discovery studies for other infectious diseases.

Nano-Based Drug Delivery or Targeting to Eradicate Bacteria for Infection Mitigation: A Review of Recent Advances.

Pathogenic bacteria infection is a major public health problem due to the high morbidity and mortality rates, as well as the increased expenditure on patient management. Although there are several options for antimicrobial therapy, their efficacy is limited because of the occurrence of drug-resistant bacteria. Many conventional antibiotics have failed to show significant amelioration in overall survival of infectious patients. Nanomedicine for delivering antibiotics provides an opportunity to improve the efficiency of the antibacterial regimen. Nanosystems used for antibiotic delivery and targeting to infection sites render some benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged antibiotic half-life, tissue targeting, and minimal adverse effects. The nanocarriers' sophisticated material engineering tailors the controllable physicochemical properties of the nanoparticles for bacterial targeting through passive or active targeting. In this review, we highlight the recent progress on the development of antibacterial nanoparticles loaded with antibiotics. We systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for bacterial eradication. Passive targeting by modulating the nanoparticle structure and the physicochemical properties is an option for efficient drug delivery to the bacteria. In addition, active targeting, such as magnetic hyperthermia induced by iron oxide nanoparticles, is another efficient way to deliver the drugs to the targeted site. The nanoparticles are also designed to respond to the change in environment pH or enzymes to trigger the release of the antibiotics. This article offers an overview of the benefits of antibacterial nanosystems for treating infectious diseases.

Laser Acupuncture Alleviates Symptoms and Improves Quality of Life in Women with Overactive Bladder: A Double-Blind, Pilot Randomized Controlled Trial.

OBJECTIVE: The aim of this study was to investigate the clinical efficacy of laser acupuncture for the treatment of women with overactive bladder (OAB) in Taiwan. METHODS: A double-blind randomized controlled trial was conducted on female patients with OAB symptoms referred from gynecologists, and subjects were divided into two groups using blocked randomization. LaserPan (RJ-Laser, Germany) was applied to seven selected acupuncture points. The subjects received laser acupuncture 3 times per week for 3 weeks, 9 sessions in total. Basic patient data, Overactive Bladder Symptom Score (OABSS), Incontinence Impact Questionnaire (IIQ-7), and Urogenital Distress Inventory (UDI-6) scores were recorded prior to first treatment and at the end of 3rd, 6th, and 9th treatments. RESULTS: Thirty patients were enrolled, and twenty-seven patients completed all treatments in this study. The OABSS total score of the experimental group decreased significantly by 3.13 (p ≤ 0.001), 4.60 (p ≤ 0.001), and 3.79 (p ≤ 0.001) after 3rd, 6th, and 9th treatments, respectively, compared with that of the control group. The IIQ-7 score declined significantly from baseline by 4.57 (p=0.003) and 3.63 (p=0.023) after 3rd and 6th treatments, respectively, compared with that of the control group. Similarly, the UDI-6 score of the experimental group exhibited a significant decrease from baseline by 1.90 (p=0.042) and 2.25 (p=0.025) after 6th and 9th interventions, respectively, compared with that of the control group. CONCLUSIONS: This study demonstrates that laser acupuncture can alleviate OAB symptoms and improve quality of life. This noninvasive device could be an effective therapy for women with OAB.

Positive Effects of Ger-Gen-Chyn-Lian-Tang on Cholestatic Liver Fibrosis in Bile Duct Ligation-Challenged Mice.

The purpose of this study was to investigate whether Ger-Gen-Chyn-Lian-Tang (GGCLT) suppresses oxidative stress, inflammation, and angiogenesis during experimental liver fibrosis through the hypoxia-inducible factor-1α (HIF-1α)-mediated pathway. Male C57BL/6 mice were randomly assigned to a sham-control or bile duct ligation (BDL) group with or without treatment with GGCLT at 30, 100, and 300 mg/kg. Plasma alanine aminotransferase (ALT) levels were analyzed using a diagnostic kit. Liver histopathology and hepatic status parameters were measured. Compared to control mice, the BDL mice exhibited an enlargement in liver HIF-1α levels, which was suppressed by 100 and 300 mg/kg GGCLT treatments (control: BDL: BDL + GGCLT-100: BDL + GGCLT-300 = 0.95 ± 0.07: 1.95 ± 0.12: 1.43 ± 0.05: 1.12 ± 0.10 fold; p < 0.05). GGCLT restrained the induction of hepatic hydroxyproline and malondialdehyde levels in the mice challenged with BDL, further increasing the hepatic glutathione levels. Furthermore, in response to increased hepatic inflammation and fibrogenesis, significant levels of ALT, nuclear factor kappa B, transforming growth factor-ß, α-smooth muscle actin, matrix metalloproteinase-2 (MMP-2), MMP-9, and procollagen-III were found in BDL mice, which were attenuated with GGCLT. In addition, GGCLT reduced the induction of angiogenesis in the liver after BDL by inhibiting vascular endothelial growth factor (VEGF) and VEGF receptors 1 and 2. In conclusion, the anti-liver fibrosis effect of GGCLT, which suppresses hepatic oxidative stress and angiogenesis, may be dependent on an HIF-1α-mediated pathway.

The anti-angiogenic effect of tryptanthrin is mediated by the inhibition of apelin promoter activity and shortened mRNA half-life in human vascular endothelial cells.

BACKGROUND: Anti-angiogenesis is an important strategy of psoriasis treatment, but the side effects of systemic agents remain difficult to overcome. Topical use of indigo naturalis ointment has been proved to improve the skin lesion of psoriasis effectively and safely and one of its major components, tryptanthrin, has been demonstrated to have anti-angiogenic effect. Apelin, which has been reported to act as an angiogenic factor that could stimulate the proliferation and migration of vascular endothelial cells and proved to be elevated in psoriasis patients, is a potential target of anti-angiogenic therapy. PURPOSE: We aim to find out if tryptanthrin works on the apelin pathway and study its anti-angiogenic mechanism. STUDY DESIGN: Human umbilical vein endothelial cells (HUVECs) were used as the in vitro model. METHODS: The effect of tryptanthrin on the expression of apelin and its receptor, APJ, was examined. The mRNA stability, promoter activity, and bioactivity of apelin, were also investigated. Migration and tube formation assay were used to evaluate the relationship between tryptanthrin and apelin. PD98059 and wortmannin were used to study the role of ERK1/2 MAPK and PI3K in apelin signaling pathway. RESULTS: We demonstrated that tryptanthrin could inhibit the expression of apelin, attenuated the stability of apelin mRNA, and significantly inhibited the apelin promoter activity. The addition of apelin-13 restored the suppression of tube formation and migration by tryptanthrin. Both PD98059 and wortmannin could down-regulate the apelin mRNA expression suggesting the important signaling role of ERK1/2 MAPK and PI3K in the gene expression of apelin. CONCLUSION: The anti-angiogenic effect of tryptanthrin was mediated by down-regulating apelin gene expression through suppression of promoter activity and decrease of mRNA stability in human vascular endothelial cells.

The atopic dermatitis-like lesion and the associated MRSA infection and barrier dysfunction can be alleviated by 2,4-dimethoxy-6-methylbenzene-1,3-diol from Antrodia camphorata.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disease with an associated barrier dysfunction and Staphylococcus aureus infection. The mainstay steroid and calcineurin inhibitor therapy shows some adverse effects. 2,4-Dimethoxy-6-methylbenzene-1,3-diol (DMD) is a benzenoid isolated from Antrodia camphorata. OBJECTIVE: We investigated the inhibitory effect of DMD on methicillin-resistant S. aureus (MRSA), the chemokine production in stimulated keratinocytes, and the AD-like lesion found in ovalbumin (OVA)-sensitized mice. METHODS: The antimicrobial effect and cutaneous barrier function were evaluated using an in vitro culture model and an in vivo mouse model of AD-like skin. RESULTS: DMD exhibited a comparative minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against MRSA with nalidixic acid, a conventional antibiotic. The MIC and MBC for DMD was 78.1 and 156.3 µg/ml, respectively. DMD also showed the ability to eliminate the clinical bacteria isolates with resistance to methicillin and vancomycin. The DNA polymerase and gyrase inhibition evoked by DMD for bacterial lethality was proposed. In the activated keratinocytes, DMD stopped the upregulation of chemokines (CCL5 and CCL17) and increased the expression of differentiation proteins (filaggrin, involucrin, and integrin ß-1). Topical application of DMD facilely penetrated into the skin, with AD-like skin displaying 2.5-fold greater permeation than healthy skin. The in vivo assessment using the mouse model with OVA sensitization and MRSA inoculation revealed a reduction of transepidermal water loss (TEWL) and bacterial burden by DMD by about 2- and 100-fold, respectively. Differentiation proteins were also restored after topical DMD delivery. CONCLUSION: Our data demonstrated an advanced concept of AD treatment by combined barrier repair and bacterial eradication with a sole agent for ameliorating the overall complications.

Indigo naturalis and its component tryptanthrin exert anti-angiogenic effect by arresting cell cycle and inhibiting Akt and FAK signaling in human vascular endothelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Indigo naturalis has been used to treat inflammatory diseases and dermatosis, including psoriasis, since thousands of years in China. It has been proven effective in our previous clinical studies on treating psoriasis, but the active component and the mechanism of how indigo naturalis working still needs to be clarified. Since the dysregulated angiogenesis is known to play an important role in the pathogenesis of psoriasis, the anti-angiogenic effect of indigo naturalis and tryptanthrin, a pure component of indigo naturalis, was investigated. MATERIALS AND METHODS: The in vivo angiogenesis was studied by chick chorioallantoic membrane assay. The in vitro studies were performed using human vascular endothelial cells. Cell viability was determined by MTT assay. Cell cycle distribution was revealed by flow cytometry. The cellular messenger (m)RNA or protein expression level was analyzed by real-time RT-PCR or Western blot, respectively. Transwell filter migration assay and matrix gel-induced tube formation method were applied to examine the angiogenic potential. RESULTS: Indigo naturalis significantly inhibited the in vivo vascular endothelial growth factor (VEGF)-induced angiogenesis, as well as tryptanthrin. In vitro studies confirmed that indigo naturalis and tryptanthrin reduced the number of viable vascular endothelial cells. Tryptanthrin resulted in a cell cycle arrest and dose-dependently decreased the expressions of cyclin A, cyclin B, cyclin dependent kinase(CDK) 1 and 2, but not cyclin D and cyclin E, at both the mRNA and protein levels. The migration and tube formation of vascular endothelial cells were significantly inhibited by tryptanthrin in a dose-dependent manner. Result also showed that tryptanthrin could reduce the phosphorylated levels of both protein kinase B (PKB or Akt) and focal adhesion kinase (FAK). CONCLUSIONS: All together, these results demonstrated the anti-angiogenic effect of tryptanthrin, the acting component of indigo naturalis and revealed the underlying mechanism by inhibiting the cell cycle progression, cell migration and tube formation, likely mediated through blocking the Akt and FAK pathways.

Hedyotis diffusa Combined with Scutellaria barbata Are the Core Treatment of Chinese Herbal Medicine Used for Breast Cancer Patients: A Population-Based Study.

Traditional Chinese medicine (TCM), which is the most common type of complementary and alternative medicine (CAM) used in Taiwan, is increasingly used to treat patients with breast cancer. However, large-scale studies on the patterns of TCM prescriptions for breast cancer are still lacking. The aim of this study was to determine the core treatment of TCM prescriptions used for breast cancer recorded in the Taiwan National Health Insurance Research Database. TCM visits made for breast cancer in 2008 were identified using ICD-9 codes. The prescriptions obtained at these TCM visits were evaluated using association rule mining to evaluate the combinations of Chinese herbal medicine (CHM) used to treat breast cancer patients. A total of 37,176 prescriptions were made for 4,436 outpatients with breast cancer. Association rule mining and network analysis identified Hedyotis diffusa plus Scutellaria barbata as the most common duplex medicinal (10.9%) used for the core treatment of breast cancer. Jia-Wei-Xiao-Yao-San (19.6%) and Hedyotis diffusa (41.9%) were the most commonly prescribed herbal formula (HF) and single herb (SH), respectively. Only 35% of the commonly used CHM had been studied for efficacy. More clinical trials are needed to evaluate the efficacy and safety of these CHM used to treat breast cancer.

Isolated Langerhans cell histiocytosis of the thyroid in a female infant.

Langerhans cell histiocytosis (LCH) involving the thyroid is very rare. It can be easily confused with far more common benign goiters or thyroid neoplasms. We report on a 5-month-old female patient presenting with progressive enlargement of an anterior neck mass. This patient underwent left subtotal thyroidectomy following which a diagnosis of isolated LCH involving the thyroid gland was confirmed. A course of chemotherapy was administered, and oral thyroxine replacement was initiated. Eighteen months after this treatment, the patient remained in complete remission. Following a thorough review of the literature, as best we are aware, this patient is the youngest individual suffering LCH who has been reported in the literature. In conclusion, isolated LCH of the thyroid is rare, and its diagnosis can be challenging for a clinician and typically requires appropriate awareness. Local excision is the treatment of choice, and prolonged follow-up is recommended.