The Construction and Application of a New Screening Method for Phosphodiesterase Inhibitors.

Phosphodiesterases (PDEs), a superfamily of enzymes that hydrolyze cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), are recognized as a therapeutic target for various diseases. However, the current screening methods for PDE inhibitors usually experience problems due to complex operations and/or high costs, which are not conducive to drug development in respect of this target. In this study, a new method for screening PDE inhibitors based on GloSensor technology was successfully established and applied, resulting in the discovery of several novel compounds of different structural types with PDE inhibitory activity. Compared with traditional screening methods, this method is low-cost, capable of dynamically detecting changes in substrate concentration in live cells, and can be used to preliminarily determine the type of PDEs affected by the detected active compounds, making it more suitable for high-throughput screening for PDE inhibitors.

Near-complete recycling of real mix electroplating sludge as valuable metals via Fe/Cr co-crystallization and stepwise extraction route.

In electroplating sludge, iron (Fe) and aluminum (Al) are common impurities that need to be separated before recycling valuable heavy metals. However, the traditional Fe/Al separation process often leads to significant losses of heavy metals. To address this issue, a new approach was developed to sequentially separate Fe/Al and recycle chromium (Cr) and nickel (Ni) from real electroplating sludge. The sludge contained 4.5% Cr, 1.2% Al, 1.1% Ni, and 14.6% Fe. Initially, the sludge was completely dissolved in a mixture of hydrochloric and nitric acids. The resulting acid solution was then heated to 160 °C for 10 h with the addition of saccharose. This hydrothermal treatment led to the hydrolysis and crystallization of 98.3% of Fe, 31.8% of Cr, 1.1% of Al, and 4.9% of Ni, forming akaganeite-bearing particles. It was observed that the excessive amount of saccharose also improved the removal of Cr, Al, and Ni, but decreased the removal of Fe. After the hydrothermal treatment, the remaining supernatant was adjusted to different pH levels (1.9, 2.9, and 4.5, respectively), and then Al, Cr, and Ni were stepwise extracted using di-(2-ethylhexyl) phosphate acid (P204). The recycling efficiencies achieved were 97.4% for Al, 61.2% for Cr, and 89.3% for Ni. This approach provides a promising method for the stepwise separation of Fe/Al and the recycling of heavy metals from electroplating sludge.

Desquamative interstitial pneumonia: A case report.

Diffuse cystic lung diseases (DCLDs) are a group of heterogeneous lung diseases that are characterized by inflated spaces or cysts within the lung parenchyma. They also exhibit similar imaging characteristics and clinical manifestations compared with those of cystic lesions, such as pulmonary cavities, emphysema, bronchiectasis and honeycomb lung. The most common DCLDs encountered in the clinic include lymphangioleiomyomatosis, Birt-Hogg-Dubé syndrome, Langerhans cell histiocytosis and lymphocytic interstitial pneumonia. In particular, accurate diagnosis of DCLDs in terms of the different lesions found is important, because their clinical courses, prognoses and treatment strategies vary widely. However, because DCLDs usually have overlapping clinical presentations, diagnosis typically requires a combination of clinical considerations that take into account characteristics of the cyst, its distribution, organ of origin and background parenchymal findings. The present report documents the case of a 73-year-old man diagnosed with desquamative interstitial pneumonia (DIP). The patient was admitted to the hospital due to chest tightness, shortness of breath and intermittent fever. The patient had been a smoker for >60 years and had stopped smoking for 6 months before being admitted. A transbronchial lung biopsy, bronchoscopy and alveolar lavage cytopathogen culture were performed to confirm the diagnosis of desquamative interstitial pneumonia (DIP). The patient was treated with hormonal therapy and advised to abstain from smoking. The diagnosis of DIP in comparison with other DCLDs was summarized for the purpose of providing a clinical basis for the accurate clinical diagnosis of DIP and the development of evidence-based practice guidelines.

The expression of VISTA on CD4+ T cells associate with poor prognosis and immune status in non-small cell lung cancer patients.

Besides the two main histologic types of papillary thyroid carcinoma (PTC), the classical PTC (CL-PTC) and the follicular variant PTC (FV-PTC), several other variants are described. The encapsulated FV-PTC variant was recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) due to its similarities to benign lesions. Specific molecular signatures, however, are still unavailable. It is well known that improper DNA repair of dysfunctional telomeres may cause telomere-related genome instability. The mechanisms involved in the damaged telomere repair processing may lead to detrimental outcomes, altering the three-dimensional (3D) nuclear telomere and genome organization in cancer cells. This pilot study aimed to evaluate whether a specific 3D nuclear telomere architecture might characterize NIFTP, potentially distinguishing it from other PTC histologic variants. Our findings demonstrate that 3D telomere profiles of CL-PTC and FV-PTC were different from NIFTP and that NIFTP more closely resembles follicular thyroid adenoma (FTA). NIFTP has longer telomeres than CL-PTC and FV-PTC samples, and the telomere length of NIFTP overlaps with that of the FTA histotype. In contrast, there was no association between BRAF expression and telomere length in all tested samples. These preliminary findings reinforce the view that NIFTP is closer to non-malignant thyroid nodules and confirm that PTC features short telomeres.

Role of Proximal Intestinal Glucose Sensing and Metabolism in the Blood Glucose Control in Type 2 Diabetic Rats After Duodenal Jejunal Bypass Surgery.

BACKGROUND: Although gastric surgery can significantly improve blood glucose homeostasis in type 2 diabetes mellitus (T2DM), its mechanism remains unclear. This study evaluated the role of intestinal glucose sensing, glucose transport, and metabolism in the alimentary limb (A limb) of T2DM rats after duodenal jejunal bypass (DJB) surgery. METHODS: A T2DM rat model was induced via a high-glucose high-fat diet and low-dose streptozotocin injection. The diabetic rats were divided into two groups: the DJB surgery (T2DM-DJB) group and the sham surgery (T2DM-Sham) group. Wistar rats were used as wild-type control (Control). Small animal PET was used to assess the change in glucose metabolic status in the intestine. The intestinal villi height and the number of EECs after DJB were evaluated. The expressions of sweet taste receptors (T1R2/T1R3), glucose transporters (SGLT1/GLUT2), and key enzymes involved in glucose metabolism (HK2, PFK2, PKM2, G6Pase, and PCK1) in the A limb after DJB was detected by Western blot and qRT-PCR. RESULTS: Small animal PET analysis showed the intestinal glucose metabolism increased significantly 6 weeks after DJB surgery. The intestinal villi height and the number of EECs in the A limb 6 weeks after surgery increased significantly in T2DM-DJB rats comparing to T2DM-Sham rats. The mRNA and protein expression of T1R1/T1R3 and SGLT1/GLUT2 were downregulated in DJB-T2DM rats, while enzymes involved in glucose metabolism was upregulated in the A limb in T2DM-DJB rats. CONCLUSION: Proximal intestinal glucose sensing and metabolism play an important role in blood glucose homeostasis by DJB.

XPC Protein Improves Lung Adenocarcinoma Prognosis by Inhibiting Lung Cancer Cell Stemness.

Objective: Xeroderma Pigmentosum Complementation Group C (XPC) is a protein involving in nucleotide excision repair (NER). XPC also plays an important role in the lung cancer occurrence with the mechanism remian unclear up to date. Studies showed that the increased stemness of lung cancer cells is related to the recurrence and metastasis of lung cancer. This study aimed to study and analyze the correlation of XPC with lung cancer stem cell biomarkers expression and the overall survival (OS) of lung adenocarcinoma patients. Methods: 140 cases of clinical lung adenocarcinoma tissue samples and 48 cases of paired paracancerous tissue samples were made into tissue microarray. Immunohistochemistry (IHC) was used to detect the expression of XPC and CD133 in cancer and paracancerous tissues. Semi-quantitative analysis and statistics were performed by Pannoramic Digital Slide Scanner. The expression of XPC and CD133 in fresh tissues was verified by Western blotting assay. siXPC was used to knock down XPC in lung cancer cell lines to study the effect of XPC on the expression of lung cancer stem cell biomarkers and the ability of cell invasion. And shXPC was used to knockdown XPC in A549 and H1650 to study the effect of XPC on the expression of lung cancer stem cell biomarkers. Results: IHC and Western blotting results showed that XPC expression significantly decreased, while CD133 expression significantly increased in cancer tissues comparing to paracancerous tissues (P XPC < 0.0001, P CD133 = 0.0395). The high level of XPC in cancer was associated with a better prognosis (Log-rank p = 0.0577) in lung adenocarcinoma patients. Downregulation of XPC in lung cancer cells showed increased expression of cancer stem cell biomarkers and the increased cell invasion abilities. Conclusion: It is suggested that XPC can exert the ability of anti-tumor formation, tumor invasion and metastasis inhibition, and prognostic survival improvement in lung adenocarcinoma patients by regulating the stemness of lung cancer cells.

Leeches attenuate blood hyperviscosity and related metabolic disorders in rats differently than aspirin.

ETHNOPHARMACOLOGICAL RELEVANCE: Whitmania pigra Whitman (Whitmania pigra, WP), firstly recorded in the Shennong's Herbal Classic and officially listed in the Chinese Pharmacopoeia, is a well-used cardiovascular protective traditional Chinese medicine derived from leeches. Traditional Chinese physicians prefer to prescribe the dried whole body of leech processed under high temperatures. It has been reported that dried WP remains clinically effective. However, the therapeutic mechanism has yet not be clearly elucidated. AIM OF THE STUDY: This study was designed to investigate the protective activity of the extract of WP in a high-molecular-weight dextran-induced blood hyperviscosity rat model, and to explore the role of WP in improving blood hyperviscosity related metabolic disorders and to clarify the possible mechanism of metabolic regulation. MATERIALS AND METHODS: The hemorheological parameters were measured with an automated blood rheology analyzer. Hematoxylin-eosin staining was used to observe the pathological changes in aortic tissues samples. Further, a liquid chromatography-mass-spectrometry (LC-MS)-based untargeted metabolomics approach was applied to characterize the metabolic alterations. RESULTS: WP has evident attenuating effects on blood hyperviscosity and related metabolic disorders, and the influences are distinct from those of aspirin. The results showed that WP had good effects in reducing blood viscosity and ameliorating histopathological changes in the thoracic aorta in a high molecular weight dextran-induced blood hyperviscosity rat model. The middle dose (2.5 g raw material/kg body weight) of WP exhibited effects equivalent to aspirin (100 mg/kg) on hemorheological and histopathological parameters (P > 0.05). However, when using metabolomics profiling, we found that WP could significantly improve blood hyperviscosity-related metabolic disorders and restore metabolites to normal levels; while aspirin showed little effect. With principal component analysis and orthogonal partial least-squares discriminant analysis, WP regulated many more endogenous metabolites than aspirin. With pathway enrichment analysis, the differential endogenous metabolites were involved in cysteine and methionine metabolism, TCA cycle, arachidonic acid metabolism, etc., highlighting the metabolic reprogramming potential of WP against blood hyperviscosity-induced metabolic disorders. CONCLUSIONS: The study suggest that WP has a more potent effect, but a different mechanism, than aspirin in improving either blood hyperviscosity or related metabolic disorders associated with cardio- and cerebrovascular diseases.