Parkinson's disease (PD) is one of the common long-term degenerative disorders that primarily affect motor systems. Gastrointestinal (GI) symptoms are common in individuals with PD and often present ...before motor symptoms. It has been found that gut dysbiosis to PD pathology is related to the severity of motor and non-motor symptoms in PD. Probiotics have been reported to have the ability to improve the symptoms related to constipation in PD patients. However, the evidence from preclinical or clinical research to verify the beneficial effects of probiotics for the motor functions in PD is still limited. An experimental PD animal model could be helpful in exploring the potential therapeutic strategy using probiotics. In the current study, we examined whether daily and long-term administration of probiotics has neuroprotective effects on nigrostriatal dopamine neurons and whether it can further alleviate the motor dysfunctions in PD mice. Transgenic MitoPark PD mice were chosen for this study and the effects of daily probiotic treatment on gait, beam balance, motor coordination, and the degeneration levels of dopaminergic neurons were identified. From the results, compared with the sham treatment group, we found that the daily administration of probiotics significantly reduced the motor impairments in gait pattern, balance function, and motor coordination. Immunohistochemically, a tyrosine hydroxylase (TH)-positive cell in the substantia nigra was significantly preserved in the probiotic-treated PD mice. These results showed that long-term administration of probiotics has neuroprotective effects on dopamine neurons and further attenuates the deterioration of motor dysfunctions in MitoPark PD mice. Our data further highlighted the promising possibility of the potential use of probiotics, which could be the relevant approach for further application on human PD subjects.
Self‐assembled monolayers (SAMs) offer the advantage of facile interfacial modification, leading to significant improvements in device performance. In this study, we report the design and synthesis ...of a new series of carboxylic acid‐functionalized porphyrin derivatives, namely AC‐1, AC‐3, and AC‐5, and present, for the first time, a strategy to exploit the large π‐moiety of porphyrins as a backbone for interfacing the indium tin oxide (ITO) electrode and perovskite active layer in an inverted perovskite solar cell (PSC) configuration. The electron‐rich nature of porphyrins facilitates hole transfer and the formation of SAMs, resulting in a dense surface that minimizes defects. Comprehensive spectroscopic and dynamic studies demonstrate that the double‐anchored AC‐3 and AC‐5 enhance SAMs on ITO, passivate the perovskite layer, and function as conduits to facilitate hole transfer, thus significantly boosting the performance of PSCs. The champion inverted PSC employing AC‐5 SAM achieves an impressive solar efficiency of 23.19 % with a high fill factor of 84.05 %. This work presents a novel molecular engineering strategy for functionalizing SAMs to tune the energy levels, molecular dipoles, packing orientations to achieve stable and efficient solar performance. Importantly, our comprehensive investigation has unraveled the associated mechanisms, offering valuable insights for future advancements in PSCs.
We have developed a series of new self‐assembled monolayers (SAMs) based on ZnII porphyrin for use as hole‐selective layer (HSL) in inverted perovskite solar cells (PSCs). Our study successfully demonstrates the superior performance of dual carboxylic acid functionalized porphyrins can boost the solar efficiency of PSCs. The outstanding performance of these porphyrin SAMs lies in their inherent self‐assembled properties and the presence of dual carboxylic acid groups that facilitate effective anchoring to both the ITO surface and perovskites.
BACKGROUND:The impact of gut microbiota on the regulation of host physiology has recently garnered considerable attention, particularly in key areas such as the immune system and metabolism. These ...areas are also crucial for the pathophysiology of and repair after myocardial infarction (MI). However, the role of the gut microbiota in the context of MI remains to be fully elucidated.
METHODS:To investigate the effects of gut microbiota on cardiac repair after MI, C57BL/6J mice were treated with antibiotics 7 days before MI to deplete mouse gut microbiota. Flow cytometry was applied to examine the changes in immune cell composition in the heart. 16S rDNA sequencing was conducted as a readout for changes in gut microbial composition. Short-chain fatty acid (SCFA) species altered after antibiotic treatment were identified by high-performance liquid chromatography. Fecal reconstitution, transplantation of monocytes, or dietary SCFA or Lactobacillus probiotic supplementation was conducted to evaluate the cardioprotective effects of microbiota on the mice after MI.
RESULTS:Antibiotic-treated mice displayed drastic, dose-dependent mortality after MI. We observed an association between the gut microbiota depletion and significant reductions in the proportion of myeloid cells and SCFAs, more specifically acetate, butyrate, and propionate. Infiltration of CX3CR1+ monocytes to the peri-infarct zone after MI was also reduced, suggesting impairment of repair after MI. Accordingly, the physiological status and survival of mice were significantly improved after fecal reconstitution, transplantation of monocytes, or dietary SCFA supplementation. MI was associated with a reorganization of the gut microbial community such as a reduction in Lactobacillus. Supplementing antibiotic-treated mice with a Lactobacillus probiotic before MI restored myeloid cell proportions, yielded cardioprotective effects, and shifted the balance of SCFAs toward propionate.
CONCLUSIONS:Gut microbiota–derived SCFAs play an important role in maintaining host immune composition and repair capacity after MI. This suggests that manipulation of these elements may provide opportunities to modulate pathological outcome after MI and indeed human health and disease as a whole.
PD-L1 has been widely demonstrated to contribute to failed antitumor immunity. Blockade of PD-L1 with monoclonal antibody could modulate the tumor immune environment to augment immunotherapy. PD-L1 ...expression is also detected in several types of cancer and is associated with poor prognosis. However, the prognostic role of PD-L1 in oral squamous cell carcinoma (OSCC) is still controversial. Our aim was to determine the role of PD-L1 in the prognosis of OSCC patients to identify its potential therapeutic relevance. PD-L1 immunoreactivity was analyzed by immunohistochemistry in 305 cancer specimens from primary OSCC patients. The medium follow-up time after surgery was 3.8 years (range from 0.1 to 11.1 years). The prognostic value of PD-L1 on overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models. Higher PD-L1 expression is more likely in tumor tissues of female than male OSCC patients (P = 0.0062). Patients with distant metastasis also had high PD-L1 expression (P = 0.0103). Multivariate analysis identified high PD-L1 expression as an independent risk factor in males and smokers (males: hazard ratio = 1.556, P = 0.0077; smokers: hazard ratio = 2.058, P = 0.0004). We suggest that PD-L1 expression, determined by IHC staining, could be an independent prognostic marker for OSCC patients who are male or who have a smoking habit.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this study, polycaprolactone (P) scaffolds are fabricated by 3D‐printing method, and subsequently a mixed solution of natural‐biocompatible chitosan (C), gelatin (G), and hydroxyapatite (H) is ...filled into the pores of P scaffolds. Freeze‐gelation method is then carried out to successfully form a cell‐compatible porous CGH matrix within P scaffold pores, obtaining a newly fabricated scaffold called CGH/P composite scaffold which has large specific surface area favorable for cell attachment and growth. The effects of slow cooling (sc) and fast cooling (fc) modes utilized in freeze process on pore structures of CGH matrix are observed via SEM. The use of fc mode creates a CGH matrix with a laminar structure which benefits nutrient permeation and cell migration. Mechanical properties tests indicate that the maximum compressive strength and Young's modulus of CGH/P‐fc scaffolds are 2–7 and 15–35 MPa, respectively. Cell compatibility tests show that on day 7, the cell numbers in the CGH/P‐fc scaffolds are about twofold of those in the P scaffolds, and the cell activities in the CGH/P‐fc scaffolds are even higher, indicating that the presence of laminar porous CGH matrix within P scaffold pores substantially enhances the migration, attachment, and growth of cells in the scaffolds. The results suggest that the fabricated CGH/P‐fc composite scaffold is highly promising for biomedical applications such as bone repair in the future.
A schematic diagram of fabricating C/P, CG/P, and CGH/P porous composite scaffolds by 3D‐printing and freeze‐gelation process.
Abstract Prostate cancer, the most frequently diagnosed malignancy in elderly males of the United States, has become a major health issue in Asia. Previous studies have demonstrated that leaf ...extracts of Toona sinensis Roem. contain cytotoxic activity on several cancer cells including prostate cancer cells. In this study, gallic acid is identified as the major anti-cancer compound in T. sinensis leaf extracts. It is cytotoxic to DU145 prostate cancer cells, through generation of reactive oxygen species (ROS) and mitochondria-mediated apoptosis, which were reversed by antioxidants catalase and N -acetylcysteine. Furthermore, gallic acid is shown to block the growth of DU145 cells at G2/M phases by activating Chk1 and Chk2 and inhibiting Cdc25C and Cdc2 activities. In addition, gallic acid has a synergistic effect with doxorubicin in suppressing the growth of DU145 cells. Taken together, our results suggest that gallic acid has the potential to be developed into an anti-prostate cancer drug and is worthy of further studies.
The long noncoding RNA HOTAIR plays significant roles in promoting cancer metastasis. However, how it conveys an invasive advantage in cancer cells is not clear. Here we identify the chondroitin ...sulfotransferase CHST15 (GalNAc4S‐6ST) as a novel HOX transcript antisense intergenic RNA (HOTAIR) target gene using RNA profiling and show that CHST15 is required for HOTAIR‐mediated invasiveness in breast cancer cells. CHST15 catalyzes sulfation of the C6 hydroxyl group of the N‐acetyl galactosamine 4‐sulfate moiety in chondroitin sulfate to form the 4,6‐disulfated chondroitin sulfate variant known as the CS‐E isoform. We show that HOTAIR is necessary and sufficient for CHST15 transcript expression. Inhibition of CHST15 by RNA interference abolished cell invasion promoted by HOTAIR but not on HOTAIR‐mediated migratory activity. Conversely, reconstitution of CHST15 expression rescued the invasive activity of HOTAIR‐depleted cells. In corroboration with this mechanism, blocking cell surface chondroitin sulfate using a pan‐CS antibody or an antibody specifically recognizes the CS‐E isoform significantly suppressed HOTAIR‐induced invasion. Inhibition of CHST15 compromised tumorigenesis and metastasis in orthotopic breast cancer xenograft models. Furthermore, the expression of HOTAIR closely correlated with the level of CHST15 protein in primary as well as metastatic tumor lesions. Our results demonstrate a novel mechanism underlying the function of HOTAIR in tumor progression through programming the context of cell surface glycosaminoglycans. Our results further establish that the invasive and migratory activities downstream of HOTAIR are distinctly regulated, whereby CHST15 preferentially controls the arm of invasiveness. Thus, the HOTAIR‐CHST15 axis may provide a new avenue toward novel therapeutic strategies and prognosis biomarkers for advanced breast cancer.
What's new?
The long noncoding RNA HOTAIR is known to influence cancer growth, and now researchers have identified a molecule that mediates the effect. Using both loss‐of‐function and gain‐of‐function experiments, these authors identified chondroitin sulfotransferase (CHST15) as a downstream target of HOTAIR required for invasive activity of breast cancer cells. Antibodies against cell surface chondroitin sulfate suppressed HOTAIR‐induced invasion in xenograft models. Further, HOTAIR expression correlates with CHST15 protein both in primary tumors and metastases. The identification of HOTAIR‐CHST15 regulation of cell surface moieties could lead to new therapeutic targets or diagnostic biomarkers for breast cancer.
Background
The eighth edition of the American Joint Committee on Cancer (AJCC) staging system for lung cancer adopts new criteria for tumor size, and for determining pTis, pT1a(mi), and pT1a. The ...latter is based on the size of stromal invasion. It is quite challenging for lung pathologists.
Methods
All patients who had undergone surgical resection for pulmonary adenocarcinoma (ADC) at Chung Shan Medical University Hospital between January 2014 and April 2018 were reviewed, and restaged according to the eighth AJCC staging system. The clinical characteristics and survival of patients with tumor stage 0 (pTis), I or II were analyzed.
Results
In total, 376 patients were analyzed. None of the pTis, pT1a(mi), or pT1a tumors recurred during the follow‐up period up to 5 years, but pT1b, pT1c, pT2a, and pT2b tumors all had a few tumor recurrences (p < 0.0001). In addition, 95.2%, 100%, and 77.5% of pTis, pT1a(mi), and pT1a tumors, respectively, had tumor sizes ≤1.0 cm by gross examination. All pTis, pT1a(mi), and pT1a tumors exhibited only lepidic, acinar, or papillary patterns histologically.
Conclusions
This study demonstrated excellent survival for lung ADC patients with pTis, pT1a(mi), and pT1a tumors when completely excised. To reduce the inconsistencies between pathologists, staging lung ADC with tumors of ≤1 cm in size grossly as pTis, pT1a(mi), or pT1a may not be necessary when the tumors exhibit only lepidic, acinar, or papillary histological patterns. A larger cohort study with sufficient follow‐up data is necessary to support this proposal.
This study demonstrated excellent survival for lung ADC patients with pTis, pT1a(mi), and pT1a tumors when completely excised. To reduce the inconsistencies between pathologists, staging lung ADC with tumors of ≤1 cm in size grossly as pTis, pT1a(mi), or pT1a may not be necessary when the tumors exhibit only lepidic, acinar, or papillary histological patterns. A larger cohort study with sufficient follow‐up data is necessary to support this proposal.
Speeded-Up Robust Features (SURF) is a robust and useful feature detector for various vision-based applications but it is unable to detect symmetrical objects. This paper proposes a new symmetrical ...SURF descriptor to enrich the power of SURF to detect all possible symmetrical matching pairs through a mirroring transformation. A vehicle make and model recognition (MMR) application is then adopted to prove the practicability and feasibility of the method. To detect vehicles from the road, the proposed symmetrical descriptor is first applied to determine the region of interest of each vehicle from the road without using any motion features. This scheme provides two advantages: there is no need for background subtraction and it is extremely efficient for real-time applications. Two MMR challenges, namely multiplicity and ambiguity problems, are then addressed. The multiplicity problem stems from one vehicle model often having different model shapes on the road. The ambiguity problem results from vehicles from different companies often sharing similar shapes. To address these two problems, a grid division scheme is proposed to separate a vehicle into several grids; different weak classifiers that are trained on these grids are then integrated to build a strong ensemble classifier. The histogram of gradient and SURF descriptors are adopted to train the weak classifiers through a support vector machine learning algorithm. Because of the rich representation power of the grid-based method and the high accuracy of vehicle detection, the ensemble classifier can accurately recognize each vehicle.
Background/purpose The National Health Insurance Research Database, which uses claims data from hospitals contracted with the National Health Insurance (NHI) program in Taiwan, has been widely used ...for stroke research. The diagnostic accuracy of the NHI claims data with regard to acute ischemic stroke (AIS) has rarely been validated. The aim of this study was to validate the diagnosis of AIS in NHI claims data using the Taiwan Stroke Registry (TSR) as a reference. Methods We retrieved patients' data with a discharge diagnosis of AIS five-digit International Classification of Diseases Code, 9th version (ICD-9 code): 433 xx or 434 xx in a single medical center from August 2006 to December 2008. We then linked these patients to the TSR to validate their AIS diagnosis in the claims data. The positive predictive value (PPV) and sensitivity were determined. Results We reviewed the claims data of 1736 consecutive AIS patients, of whom 1299 (74.8%) were linked successfully to the stroke registry database. After reviewing the medical records and imaging results of other patients not linked to the registry database ( n = 437), 235 patients were found to have had an AIS. The PPV was 88.4% 95% confidence interval (CI): 86.8–89.8% and sensitivity was 97.3% (95% CI: 96.4–98.1%). Forty-four (21.8%) of the false-positive cases ( n = 202) were coded as 433 x 0 or 434 x 0. Conclusion The PPV of a diagnosis of AIS in the NHI claims data was high. Using five-digit ICD-9 codes to identify AIS cases will markedly decrease the false-positive rate compared with using the commonly used three-digit method.
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