Network Pharmacology and Experimental Verification to Explore the Potential Mechanism of Yin-Huo-Tang for Lung Adenocarcinoma Recurrence.

PURPOSE: Yin-Huo-Tang (YHT) is a classic traditional Chinese prescription, used to prevent lung adenocarcinoma (LUAD) relapse by "nourishing yin and clearing heat". In this study, the mechanism of YHT in LUAD recurrence was investigated. METHODS: Firstly, the bioactive compounds and targets of YHT, as well as related targets of LUAD recurrence, were collected from public databases. The protein-protein interaction network, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to find the pivotal compounds, hub genes, functional annotation and main pathways. Subsequently, RNA sequencing of recurrent tumor tissues from Lewis lung carcinoma mice treated with YHT was used to explore the main pathways. At the same time, pathways screened by network pharmacology and RNA sequencing analysis were considered the most important pathways. Finally, liquid chromatography mass spectrometry was used to validate the pivotal active ingredients. Molecular docking technology was performed to validate the binding association between the hub genes and the pivotal active ingredients. PCR and WB analysis were used to validate the main pathways. RESULTS: There were 128 active compounds and 419 targets interacting with YHT and LUAD recurrence. Network analysis identified 4 pivotal compounds, 28 hub genes and 30 main pathways. Sphingolipid signaling pathway was the common main pathway in network pharmacology and RNA sequencing results. The hub gene related to the sphingolipid signaling pathway was S1PR5. Qualitative phytochemical analysis confirmed the presence of 3 pivotal compounds, namely stigmasterol, nootkatone and ergotamine. The molecular docking verified that the pivotal compounds could good affinity with S1PR5. The PCR and WB analysis verified YHT suppressed Lewis lung cancer cells proliferation and migration by inhibiting the sphingolipid signaling pathway. CONCLUSION: The potential mechanism and therapeutic effect of YHT against the recurrence of LUAD may be ascribed to inhibition of the sphingolipid signaling pathway.

Traditional Chinese Medicine Xihuang Wan Inhibited Lewis Lung Carcinoma in a Syngeneic Model, Equivalent to Cytotoxic Chemotherapy, by Altering Multiple Signaling Pathways.

BACKGROUND/AIM: Xihuang Wan (XHW), a traditional Chinese medicine (TCM), has been used in China for a variety of cancers including lung cancer. The present study evaluated the efficacy of XHW on a Lewis lung mouse model and explored the potential mechanism via transcriptomics. MATERIALS AND METHODS: The mice were randomized into 6 groups: 1) untreated control (n=10); 2) low-dose XHW; 3) medium-dose XHW; 4) high-dose XHW; 5) cisplatin; and 6) untreated blank (n=4). Lewis lung carcinoma (LLC) cells were injected subcutaneously except for the 4 mice in the blank group. The body weight and tumor length and width were measured every 3 days. RNA-sequencing was performed on tumors in the high-dose XHW group and the control group. RESULTS: XHW inhibited the growth of LLC in a syngeneic mouse model, without toxicity, with equivalent efficacy to cisplatin. RNA-sequencing demonstrated that many signaling pathways were involved in XHW-mediated inhibition of LLC, including tumor necrosis factor, estrogen, cyclic guanosine 3', 5'-monophosphate-protein kinase G, apelin and the peroxisome proliferator-activated receptor signaling pathways. CONCLUSION: XHW inhibited LLC carcinoma through different pathways and shows clinical promise for patients who cannot tolerate platinum-based drugs.

Do Different Species of Sargassum in Haizao Yuhu Decoction Cause Different Effects in a Rat Goiter Model?

Sargassum species combined with Glycyrrhiza uralensis is a famous herbal pair in traditional Chinese medicine, as one of the so-called "eighteen antagonistic medicaments." In the Chinese Pharmacopoeia, two different species of Sargassum, Sargassum pallidum and Sargassum fusiforme, are recorded but they are not clearly differentiated in clinical use. In this study, we aimed to determine whether the two species of Sargassum could result in different effects when combined with G. uralensis in Haizao Yuhu Decoction (HYD), which is used for treating thyroid-related diseases, especially goiter. HYD containing S. pallidum or S. fusiforme was administered to rats with propylthiouracil-induced goiter. After 4 weeks, pathological changes in the thyroid tissue and the relative thyroid weight indicated that HYD containing S. pallidum or S. fusiforme protected thyroid tissues from propylthiouracil damage. Neither species increased the propylthiouracil-induced decrease in serum levels of thyroid hormones. However, there were some differences in their actions, and only HYD containing S. fusiforme abated the propylthiouracil-induced elevation of serum thyroid-stimulating hormone levels and activated thyroglobulin mRNA expression.

Comparative Efficacy and Toxicity of Different Species of Sargassum in Haizao Yuhu Decoction in PTU-Induced Goiter Rats.

BACKGROUND: Haizao Yuhu Decoction has been widely used to treat thyroid-related diseases especially goiter with few side effects in traditional Chinese medicine (TCM), including herb pair Sargassum (HZ) and Glycyrrhizae Radix et Rhizoma (GC), as one of "eighteen antagonistic medicaments." The two different species of Sargassum, Sargassum fusiforme (Sf) and Sargassum pallidum (Sp), are not clearly differentiated in clinical use, so that herb pair Sf-GC and Sp-GC could show different effect and toxicity. METHODS: We investigated the antigoitrous effect and toxicity and clarified the potential underlying mechanism of the two different species of Sargassum in HYD (HYDf and HYDp) in PTU-reduced goiter rats. RESULTS: The results demonstrated that both HYDf and HYDp could exhibit antigoitrous effect through alterations in hypothalamus-pituitary-thyroid (HPT) axis and inhibition of the TPO gene expression; there is no difference in the antigoitrous effects between the two different species of Sargassum application in HYD. CONCLUSION: This study evaluated the safety and efficacy of herb pair HZ-GC applied in HYD in goiter rats at molecular, cellular, and whole level and compared the two species of Sargassum further. We provide a reliable way to clarify the possible mechanism of the antagonistic medicament herb pair HZ-GC for its application.

Update on sarcoidosis.

PURPOSE OF REVIEW: Sarcoidosis is a multisystem inflammatory disease, characterized by the presence of noncaseating granulomas. Ocular inflammation is often the first manifestation of the disease, and uveitis can be the driving force for treatment. The goal of this review was to provide an update on the relationship between ocular and systemic disease, with a particular focus on cardiac sarcoidosis. RECENT FINDINGS: Chest radiograph remains the best imaging tool for sarcoidosis, although newer modalities, such as whole-body PET scan, cardiac MRI, and chest computed tomography (CT), may provide additional valuable information in select populations. Ocular sarcoidosis is a marker for vascular endothelial dysfunction and increased arterial rigidity. Choroidal involvement is associated with an increased risk of cardiac disease requiring intervention. Cardiac disease continues to be underdiagnosed in patients with sarcoidosis, although it remains a leading cause of death. SUMMARY: Sarcoidosis is a systemic disease, and ophthalmologists should continually assess patients for extraocular manifestations. Although no screening guidelines exist, baseline ECGs on asymptomatic patients might identify those at risk for adverse cardiac events. Patients with symptoms of cardiac disease, including palpitations, chest pain, and dyspnea, should have an evaluation by a cardiologist.

Anterior Segment Imaging Predicts Incident Gonioscopic Angle Closure.

PURPOSE: To investigate the incidence of gonioscopic angle closure after 4 years in subjects with gonioscopically open angles but varying degrees of angle closure detected on anterior segment optical coherence tomography (AS OCT; Visante; Carl Zeiss Meditec, Dublin, CA) at baseline. DESIGN: Prospective, observational study. PARTICIPANTS: Three hundred forty-two subjects, mostly Chinese, 50 years of age or older, were recruited, of whom 65 were controls with open angles on gonioscopy and AS OCT at baseline, and 277 were cases with baseline open angles on gonioscopy but closed angles (1-4 quadrants) on AS OCT scans. METHODS: All subjects underwent gonioscopy and AS OCT at baseline (horizontal and vertical single scans) and after 4 years. The examiner performing gonioscopy was masked to the baseline and AS OCT data. Angle closure in a quadrant was defined as nonvisibility of the posterior trabecular meshwork by gonioscopy and visible iridotrabecular contact beyond the scleral spur in AS OCT scans. MAIN OUTCOME MEASURES: Gonioscopic angle closure in 2 or 3 quadrants after 4 years. RESULTS: There were no statistically significant differences in age, ethnicity, or gender between cases and controls. None of the control subjects demonstrated gonioscopic angle closure after 4 years. Forty-eight of the 277 subjects (17.3%; 95% confidence interval [CI], 12.8-23; P < 0.0001) with at least 1 quadrant of angle closure on AS OCT at baseline demonstrated gonioscopic angle closure in 2 or more quadrants, whereas 28 subjects (10.1%; 95% CI, 6.7-14.6; P < 0.004) demonstrated gonioscopic angle closure in 3 or more quadrants after 4 years. Individuals with more quadrants of angle closure on baseline AS OCT scans had a greater likelihood of gonioscopic angle closure developing after 4 years (P < 0.0001, chi-square test for trend for both definitions of angle closure). CONCLUSIONS: Anterior segment OCT imaging at baseline predicts incident gonioscopic angle closure after 4 years among subjects who have gonioscopically open angles and iridotrabecular contact on AS OCT at baseline.

Changes in anterior segment dimensions over 4†years in a cohort of Singaporean subjects with open angles.

AIM: To evaluate quantitative changes in anterior segment optical coherence tomography (AS-OCT) parameters at 4 years in subjects with open angles on gonioscopy at baseline. METHODS: 339 gonioscopically open-angle subjects aged >50 years underwent AS-OCT imaging (Visante, Carl Zeiss Meditec, Dublin, California, USA) at baseline and at 4 years. Customised software was used to analyse images. Linear regression was performed to assess baseline predictors of change in mean trabecular iris space area (TISA). RESULTS: Of the 339 subjects, 204 (61%) had good images for analysis. The mean age at baseline was 60 (SD 6.42) years; 55.4% were women and 87.7% were Chinese. Overall, there was a decrease in anterior chamber depth (ACD), anterior chamber area (ACA), anterior chamber volume (ACV) and angle opening distance at 500/750 µm, TISA 500/750 µm, iris thickness at 2000 µm and iris area in both nasal and temporal quadrants (p<0.05) at 4 years. There was an increase in iris curvature (ICURV) and lens vault (LV) (p<0.05). With univariate analysis, shorter axial length (AxL), shallower ACD, greater LV, smaller ACA/ACV and larger mean ICURV at baseline were associated with less change in TISA750 at follow-up. On multivariate analysis, only baseline mean ICURV and shorter AxL were predictive of less change in TISA750 at 4 years. CONCLUSIONS: Angle width significantly decreased; ICURV and LV increased in subjects with gonioscopically open angles followed at 4 years. Eyes with shorter AxL and greater ICURV at baseline had lesser decrease in angle width.

Clinical features and incidence rate of ocular complications in punctate inner choroidopathy.

PURPOSE: To study the clinical features and incidence rate of ocular complications in patients with punctate inner choroidopathy. METHODS: This is a retrospective cohort study conducted in a single-center academic practice setting. Patients diagnosed with punctate inner choroidopathy at the Wilmer Eye Institute, Johns Hopkins University from 1984 to 2012 were identified. Demographics and clinical features including the presence of choroidal neovascularization (CNV) and structural complications were collected. Main outcome measures, including visual impairment and incidence rate of ocular complications, were analyzed. RESULTS: Thirty-one patients (59 eyes) were included in the study. Follow-up data were available for 24 patients (47 eyes) with a mean follow-up time of 3.4 years (range, 2 months to 8.7 years). In the affected eyes with follow-up, the incidence rate of visual impairment to 20/50 or worse was 0.06 per eye-year (EY) (95% confidence interval, 0.022/EY-0.114/EY). The incidence rate of visual loss to 20/200 or worse was 0.006/EY (95% confidence interval, 0.0001/EY-0.034/EY). Thirty-six eyes (77%) had an ultimate visual acuity of 20/40 or better. All of the 13 patients with more than ≥ 3 years of follow-up had a visual acuity of ≥ 20/40 in at least 1 eye at 3 years after presentation. Two thirds of the follow-up patients (67%) on immunomodulatory drug therapy did not have new or recurrent CNV. However, this was not a statistically significant difference. Three eyes with follow-up had recurrence of CNV for an incidence rate of 0.04/EY (95% confidence interval, 0.008/EY-0.12/EY). Two eyes developed new CNV during follow-up for an incidence rate of 0.02/EY (95% confidence interval, 0.002/EY-0.066/EY). CONCLUSION: The visual prognosis in most cases of punctate inner choroidopathy is very good. The incidence rate of new CNV and recurrent CNV was 0.02/EY and 0.04/EY, respectively.

The rare case of cervical rib fusion to the second rib.

This article reports on 3 patients who presented with arterial thoracic outlet syndrome and were found to have a rare clinical entity. All 3 patients presented with a rare cervical rib, which was also found to be fused to the second rib, with no first rib at all. All underwent transaxillary cervical and second rib resections and anterior scalenectomy. After transaxillary thoracic outlet decompression, all completed physical therapy with complete resolution of symptoms.

Bilateral vision loss associated with radiofrequency exposure.

A 57-year-old otherwise healthy woman presented with painless binocular vision loss 1 week after direct application of radiofrequency energy to her orbits. She had no light perception bilaterally. Pupils were dilated and not reactive to light. Fundoscopic exam initially showed optic disc swelling in the right eye and a normal-appearing disc in the left eye. Magnetic resonance imaging of the brain and orbits showed gadolinium enhancement of both intraorbital optic nerves. She underwent a course of high-dose steroid treatment without recovery of vision. Optic discs were pale 11 weeks after injury. With exclusion of other possible causes, this represents a unique case of irreversible binocular optic nerve damage and blindness secondary to radiofrequency exposure.

Adiponectin activates AMP-activated protein kinase in muscle cells via APPL1/LKB1-dependent and phospholipase C/Ca2+/Ca2+/calmodulin-dependent protein kinase kinase-dependent pathways.

The binding of the adaptor protein APPL1 to adiponectin receptors is necessary for adiponectin-induced AMP-activated protein kinase (AMPK) activation in muscle, yet the underlying molecular mechanism remains unknown. Here we show that in muscle cells adiponectin and metformin induce AMPK activation by promoting APPL1-dependent LKB1 cytosolic translocation. APPL1 mediates adiponectin signaling by directly interacting with adiponectin receptors and enhances LKB1 cytosolic localization by anchoring this kinase in the cytosol. Adiponectin also activates another AMPK upstream kinase Ca2+/calmodulin-dependent protein kinase kinase by activating phospholipase C and subsequently inducing Ca2+ release from the endoplasmic reticulum, which plays a minor role in AMPK activation. Our results show that in muscle cells adiponectin is able to activate AMPK via two distinct mechanisms as follows: a major pathway (the APPL1/LKB1-dependent pathway) that promotes the cytosolic localization of LKB1 and a minor pathway (the phospholipase C/Ca2+/Ca2+/calmodulin-dependent protein kinase kinase-dependent pathway) that stimulates Ca2+ release from intracellular stores.

Needle-based reflection refractometry of scattering samples using coherence-gated detection.

We present a novel method for in situ refractive index measurement of scattering samples using a needle device. The device employs a fiber-based reflectance refractometer and coherence-gated detection of the reflected optical signal that eliminates scattering-dependent backreflection contributions. Additionally, birefringence changes induced by fiber movement are neutralized by randomizing the source polarizations and averaging the measured Fresnel reflection coefficients over many incident polarization states. Experimental measurements of Intralipid scattering solutions are presented and compared with Monte Carlo simulations.