Preoperative blood markers and intra-abdominal infection after colorectal cancer resection.

BACKGROUND: Colorectal cancer (CRC) has one of the highest morbidity and mortality rates among digestive tract tumors. Intra-abdominal infection (IAI) is a common postoperative complication that affects the clinical outcomes of patients with CRC and hinders their rehabilitation process. However, the factors influencing abdominal infection after CRC surgery remain unclear; further, prediction models are rarely used to analyze preoperative laboratory indicators and postoperative complications. AIM: To explore the predictive value of preoperative blood markers for IAI after radical resection of CRC. METHODS: The data of 80 patients who underwent radical resection of CRC in the Anorectal Surgery Department of Suzhou Hospital affiliated with Anhui Medical University were analyzed. These patients were categorized into IAI (n = 15) and non-IAI groups (n = 65) based on whether IAI occurred. Influencing factors were compared; general data and laboratory indices of both groups were identified. The relationship between the indicators was assessed. Further, a nomogram prediction model was developed and evaluated; its utility and clinical applicability were assessed. RESULTS: The risk factors for IAI after radical resection of CRC were neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and carcinoembryonic antigen (CEA) levels. NLR was correlated with PLR and SII (r = 0.604, 0.925, and 0.305, respectively), while PLR was correlated with SII (r = 0.787). The nomogram prediction model demonstrated an area under the curve of 0.968 [95% confidence interval (CI): 0.948-0.988] in the training set (n = 60) and 0.926 (95%CI: 0.906-0.980) in the validation set (n = 20). The average absolute errors of the calibration curves for the training and validation sets were 0.032 and 0.048, respectively, indicating a good model fit. The decision curve analysis curves demonstrated high net income above the 5% threshold, indicating the clinical practicality of the model. CONCLUSION: The nomogram model constructed using NLR, PLR, SII, and CEA levels had good accuracy and reliability in predicting IAI after radical resection of CRC, potentially aiding clinical treatment decision-making.

KLF10/CBS increases the sensitivity of gastric carcinoma cells to methionine restriction by promoting sulfur transfer pathway.

Gastric cancer metastasis is a major cause of poor prognosis. Our previous research showed that methionine restriction (MR) lowers the invasiveness and motility of gastric carcinoma. In this study, we investigated the particular mechanisms of MR on gastric carcinoma metastasis. In vitro, gastric carcinoma cells (AGS, SNU-5, MKN7, KATO III, SNU-1, and MKN45) were grown in an MR medium for 24 h. In vivo, BALB/c mice were given a methionine-free (Met-) diet. Transwell assays were used to investigate cell invasion and migration. The amounts of Krüppel like factor 10 (KLF10) and cystathionine ß-synthase (CBS) were determined using quantitative real-time PCR and Western blot. To determine the relationship between KLF10 and CBS, chromatin immunoprecipitation and a dual-luciferase reporter experiment were used. Hematoxylin-eosin staining was used to detect lung metastasis. Liquid chromatography-mass spectrometry was used to determine cystathionine content. MR therapy had varying effects on the invasion and migration of gastric carcinoma cells AGS, SNU-5, MKN7, KATO III, SNU-1, and MKN45. KLF10 was highly expressed in AGS cells but poorly expressed in KATO III cells. KLF10 improved MR's ability to prevent gastric carcinoma cell invasion and migration. In addition, KLF10 may interact with CBS, facilitating transcription. Further detection revealed that inhibiting the KLF10/CBS-mediated trans-sulfur pathway lowered Met-'s inhibitory effect on lung metastasis development. KLF10 transcription activated CBS, accelerated the trans-sulfur pathway, and increased gastric carcinoma cells' susceptibility to MR.

USP16 is an ISG15 cross-reactive deubiquitinase that targets pro-ISG15 and ISGylated proteins involved in metabolism.

Interferon-induced ubiquitin (Ub)-like modifier ISG15 covalently modifies host and viral proteins to restrict viral infections. Its function is counteracted by the canonical deISGylase USP18 or Ub-specific protease 18. Notwithstanding indications for the existence of other ISG15 cross-reactive proteases, these remain to be identified. Here, we identify deubiquitinase USP16 as an ISG15 cross-reactive protease by means of ISG15 activity-based profiling. Recombinant USP16 cleaved pro-ISG15 and ISG15 isopeptide-linked model substrates in vitro, as well as ISGylated substrates from cell lysates. Moreover, interferon-induced stimulation of ISGylation was increased by depletion of USP16. The USP16-dependent ISG15 interactome indicated that the deISGylating function of USP16 may regulate metabolic pathways. Targeted enzymes include malate dehydrogenase, cytoplasmic superoxide dismutase 1, fructose-bisphosphate aldolase A, and cytoplasmic glutamic-oxaloacetic transaminase 1. USP16 may thus contribute to the regulation of a subset of metabolism-related proteins during type-I interferon responses.

Angiopoietin4 (ANGPT4) expression and potential mechanisms in carcinogenesis: current achievements and perspectives.

Angiopoietin4(ANGPT4) which plays a significant role in endothelial cell proliferation, survival, angiogenesis and expansion in tumors and other pathological states is a significant regulator of tumor angiogenesis. ANGPT4 expression is enhanced in many cancer cells. For example, the overexpression of ANGPT4 promotes the formation, development and progress of lung adenocarcinoma, glioblastoma and ovarian cancer. Related studies show that ANGPT4 encourages the proliferation, survival and invasion of tumor cells, while promoting the expansion of the tumor vascular system and affecting the tumor immune microenvironment. ANGPT4 can also promote carcinogenesis by affecting the ERK1/2, PI3K/AKT and other signal pathways downstream of tyrosine kinase with immunoglobulin-like and EGF-like domains 2(TIE2) and TIE2. Therefore, ANGPT4 may be a potential and significant biomarker for predicting malignant tumor progression and adverse outcomes. In addition, inhibition of ANGPT4 may be a meaningful cancer treatment. This paper reviews the latest research results of ANGPT4 in preclinical research, and emphasizes its role in carcinogenesis. Additional research on the carcinogenic function of ANGPT4 could provide new insights into cancer biology and novel methods for cancer diagnosis and treatment.

Cellular Validation of a Chemically Improved Inhibitor Identifies Monoubiquitination on OTUB2.

Ubiquitin thioesterase OTUB2, a cysteine protease from the ovarian tumor (OTU) deubiquitinase superfamily, is often overexpressed during tumor progression and metastasis. Development of OTUB2 inhibitors is therefore believed to be therapeutically important, yet potent and selective small-molecule inhibitors targeting OTUB2 are scarce. Here, we describe the development of an improved OTUB2 inhibitor, LN5P45, comprising a chloroacethydrazide moiety that covalently reacts to the active-site cysteine residue. LN5P45 shows outstanding target engagement and proteome-wide selectivity in living cells. Importantly, LN5P45 as well as other OTUB2 inhibitors strongly induce monoubiquitination of OTUB2 on lysine 31. We present a route to future OTUB2-related therapeutics and have shown that the OTUB2 inhibitor developed in this study can help to uncover new aspects of the related biology and open new questions regarding the understanding of OTUB2 regulation at the post-translational modification level.

IFNÉ£ but not IFNα increases recognition of insulin defective ribosomal product-derived antigen to amplify islet autoimmunity.

AIMS/HYPOTHESIS: The inflammatory milieu characteristic of insulitis affects translation fidelity and generates defective ribosomal products (DRiPs) that participate in autoimmune beta cell destruction in type 1 diabetes. Here, we studied the role of early innate cytokines (IFNα) and late immune adaptive events (IFNÉ£) in insulin DRiP-derived peptide presentation to diabetogenic CD8+ T cells. METHODS: Single-cell transcriptomics of human pancreatic islets was used to study the composition of the (immuno)proteasome. Specific inhibition of the immunoproteasome catalytic subunits was achieved using siRNA, and antigenic peptide presentation at the cell surface of the human beta cell line EndoC-ßH1 was monitored using peptide-specific CD8 T cells. RESULTS: We found that IFNγ induces the expression of the PSMB10 transcript encoding the ß2i catalytic subunit of the immunoproteasome in endocrine beta cells, revealing a critical role in insulin DRiP-derived peptide presentation to T cells. Moreover, we showed that PSMB10 is upregulated in a beta cell subset that is preferentially destroyed in the pancreases of individuals with type 1 diabetes. CONCLUSIONS/INTERPRETATION: Our data highlight the role of the degradation machinery in beta cell immunogenicity and emphasise the need for evaluation of targeted immunoproteasome inhibitors to limit beta cell destruction in type 1 diabetes. DATA AVAILABILITY: The single-cell RNA-seq dataset is available from the Gene Expression Omnibus (GEO) using the accession number GSE218316 ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE218316 ).

Two-point fixation enhanced the outcome of laparoscopy-assisted ventriculoperitoneal shunt in adult patients with hydrocephalus: a retrospective study.

Objective: In patients with hydrocephalus, laparoscopy significantly improved ventriculoperitoneal shunt (VPS) outcomes. However, abdominal complications still occur, which require revision surgeries. In this study, we aimed to examine whether laparoscopy-assisted VPS with two-point fixation (LAVPS-TPF) has better outcomes than those of VPS (open-VPS) and laparoscopy-assisted VPS with no fixation (LAVPS-NF). Methods: We retrospectively reviewed clinical records of 105 open-VPS, 40 LAVPS-NF, and 49 LAVPS-TPF cases from 2015 to 2020. Data including body mass index, etiology, abdominal surgery history, Glasgow coma scale (GCS), operation time, in-hospital days, shunt failure, complications, and modified Rankin scores were analyzed, as well as subgroups of patients with history of abdominal surgery, GCS scores, and revision surgeries. Results: The LAVPS-TPF group demonstrated decreased shunt failure rates at 12 months (2.04%) compared to those of the open-VPS group (14.29%, P = 0.020) and reduced abdominal shunt-related complications (P = 0.004 vs. open-VPS and LAVPS-NF) and shunt revisions. In the LAVPS-TPF group with abdominal history (n = 51), 12-month shunt failure rates (P = 0.020 vs. open-VS), repair frequency (P = 0.020 vs. open-VS), and abdominal complications (P = 0.003 and 0.006 vs. open-VS and LAVPS-NF) were reduced. In the LAVPS-TPF group with GCS scores of 13-15 (n = 152), shunt failure rates at 12 months, abdominal complications, and revision frequency were decreased (P < 0.05 vs. other groups). Compared to the LAVPS-NF group, neurological complications were also reduced (P = 0.001). Among revision surgeries (n = 28), fixed shunts resulted in improved shunt survival rates at 12 months, reduced abdominal complications, and secondary revisions (P < 0.05). Moreover, a more optimal recovery without neurological sequelae was achieved by shunt fixation than that by LAVPS-NF (P < 0.01). Conclusions: LAVPS-TPF significantly improved shunt survival rates at 12 months and reduced the incidence of abdominal shunt-related complications compared to open-VPS and LAVPS-NF, especially in patients with history of abdominal surgery, higher GCS scores, and revision surgeries. However, further studies are required to confirm these benefits.

VPS72, a member of VPS protein family, can be used as a new prognostic marker for hepatocellular carcinoma.

BACKGROUND: Vacuolar protein sorting (VPS) plays a crucial role in intracellular molecular transport between organelles. However, studies have indicated a correlation between VPSs and tumorigenesis and the development of several cancers. Nevertheless, the association between VPSs and hepatocellular carcinoma (HCC) remains unclear. METHODS: By analyzing databases such as The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC), we investigated the differences in VPSs expression between normal tissue and HCC transcriptomes. Furthermore, we examined the relationship between VPSs expression and overall survival (OS) in patients with HCC. Univariate and multivariate Cox analyses were employed to assess the prognostic value of VPS72 as an independent factor, and the correlation between VPS72 and the tumor immune microenvironment was also analyzed. RESULTS: We observed significant overexpression of 28 VPSs in HCC tissues compared to normal tissues. The mRNA expression of VPSs displayed a negative correlation with OS, while exhibiting a positive correlation with tumor grade and stage. Additionally, both univariate and multivariate Cox analyses identified VPS72 as a potential independent risk factor for HCC prognosis. Overexpression of VPS72 demonstrated a positive correlation with various clinicopathological factors associated with poor prognosis, as well as the infiltration levels of immune cells. CONCLUSION: Therefore, our research shows that VPSs participate in HCC occurrence and development, especially VPS72, which may act as a potential target for HCC treatment and prognosis biomarker.

Potential Therapeutic Effects of Policosanol from Insect Wax on Caenorhabditis elegans Models of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. The standard treatments for PD focus on symptom relief rather than attempting to address the underlying degenerative processes completely. This study aimed to evaluate the potential therapeutic effects of policosanol derived from insect wax (PIW) by investigating improvements in disease symptoms represented in Caenorhabditis elegans models of PD. For our assessments, we used the following three models: NL5901, which is a transgenic model for α-synuclein aggregation; wild-type N2 induced with 6-hydroxydopamine (6-OHDA); and 6-OHDA-induced BZ555 as a model for loss of dopaminergic neurons (DNs). Specifically, we examined the effects of PIW treatment on α-synuclein aggregation, the loss of DNs, lipid abundance, and the lifespan of treated organisms. Further, we examined treatment-related changes in the levels of reactive oxygen species (ROS), malondialdehyde (MDA), adenosine triphosphate (ATP), glutathione S-transferase (GST), and superoxide dismutase (SOD), as well as the mRNA production profiles of relevant genes. A 10 µg/mL dose of PIW reduced the aggregation of α-synuclein in NL5901 and suppressed the loss of DNs in 6-OHDA-induced BZ555. Overall, PIW treatment decreased ROS and MDA levels, restored lipid abundance, and prolonged the lifespans of worms in all the three models, which may be associated with changes in the expression profiles of genes related to cell survival and oxidative stress response pathways. Our findings show that PIW alleviated the symptoms of PD in these models, possibly by regulating the stress responses initiated by injuries such as α-synuclein aggregation or 6-OHDA treatment.

Improving Effect of the Policosanol from Ericerus pela Wax on Learning and Memory Impairment Caused by Scopolamine in Mice.

Policosanol (PC) is a mixture of long-chain fatty alcohols that exhibits multiple biological activities, such as reducing blood lipid and cholesterol levels, lowering blood pressure, and extenuating liver inflammation. To assess PC's impact on cognitive behavior and function, PC was prepared from Ericerus pela wax using a reduction method and analyzed using gas chromatography (GC). A total of 60 mice were randomly divided into six groups of 10 animals each: control (0.5% CMC-Na solution, i.g.), model (0.5% CMC-Na solution, i.g.), donepezil (3 mg/kg, i.g.), PC low- (2 g/kg, i.g.), medium (4 g/kg, i.g.), and high- (6 g/kg, i.g.) dose groups. All the groups were administered daily for 28 consecutive days. There were four parameters­escape latency, crossings of platform, swimming distance, and time spent in the target quadrant­that were recorded to evaluate the cognitive performance of mice in the Morris Water Maze (MWM). After MWM testing, the levels of acetylcholine (ACh), acetylcholinesterase (AChE), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) that were present in brain tissue were determined using assay kits. The GC data showed that PC consisted of four major components: tetracosanol (14.40%), hexacosanol (48.97%), octacosanol (25.40%), and triacontanol (4.80%). In the MWM test, PC significantly decreased the escape latency (p < 0.05) and increased the crossings of the platform (p < 0.05) and swimming distance (p < 0.05) and time in the target quadrant (p < 0.05) in rodents compared to that in the model group. Moreover, PC increased the levels of ACh, SOD, and GSH; inhibited AChE; and reduced MDA in the brain tissue of the tested animals. This is the first report to evaluate the efficacy of PC for cognitive behavior and function in animals. Our findings demonstrate that PC from E. pela wax is likely to exert an enhancing effect on learning and memory by promoting the cholinergic system and attenuating oxidative stress, which will provide a new insight into the efficacy of PC and expand its application in the food, nutraceutical, and beverage industries.

Purification of polyphenols from Phyllanthus emblica L. pomace using macroporous resins: Antioxidant activity and potential anti-Alzheimer's effects.

Phyllanthus emblica L. pomace is a waste residue obtained following juicing that contains many polyphenols. In this study, NKA-II resin was selected as the optimal macroporous resin for separation and employed to separate the crude polyphenol extract of P. emblica pomace. The separation conditions were optimized, and the polyphenol content, polyphenol components, antioxidant activity, and potential anti-Alzheimer's effects of the extract were measured before and after purification. Results showed that the polyphenol content of the purified extract was 656.85 mg/g, which was 2.1 times higher than that of the nonpurified form. Further, the polyphenol components of the pomace, which was like that of the fruit, did not vary after purification. The antioxidant activity of the purified extract was also significantly improved. Moreover, purified extract significantly reduced the paralysis rate of the transgenic Caenorhabditis elegans model of Alzheimer's disease, and the mechanism was related to maintenance of redox homeostasis. PRACTICAL APPLICATION: The polyphenol content and antioxidant activity of purified polyphenol from Phyllanthus emblica L. pomace extracts were significantly improved using optimal separation methods with NKA-II macroporous resin and 70% aqueous ethanol as the eluent in this study. Moreover, purified polyphenols showed potential effects in alleviating Alzheimer's disease. These results suggest that polyphenols separated from P. emblica pomace are valuable for further research and development, and the utilization rate of P. emblica fruit is improved due to the further development of P. emblica pomace.

The Effects of Antioxidants and Packaging Methods on Inhibiting Lipid Oxidation in Deep Fried Crickets (Gryllus bimaculatus) during Storage.

This study aimed to investigate the effect of processing methods on inhibiting lipid oxidation of deep fried crickets (Gryllus bimaculatus) during storage. Four antioxidants and two packaging methods were used. The effects of different antioxidants and packaging methods on composition of fatty acids, contents of free fatty acids (FFA), peroxide value (PV), and thiobarbituric acid reactive substances (TBARSs) value of deep fried Gryllus bimaculatus were analyzed during 150 days of storage. The composition of fatty acids changed and the content of FFA, PV, and TBARs value also increased with the extension of storage time, indicating that the lipid oxidation dominated by oxidation of unsaturated fatty acids could occur in deep fried Gryllus bimaculatus during storage. In the same storage period, the total content of FFA, PV, and TBARs value of samples treated with antioxidants and vacuum-filling nitrogen packaging were lower than those of controls, suggesting that antioxidants and vacuum-filling nitrogen packaging have noticeable effects on inhibiting lipid oxidation and improving the quality of deep fried crickets, and dibutyl hydroxyl toluene (BHT) was found as the most effective antioxidant in this study. The results may provide a reliable reference for processing of deep fried edible insects.

Exosome-mediated transfer of lncRNA HCG18 promotes M2 macrophage polarization in gastric cancer.

BACKGROUND: Gastric cancer (GC) derived exosomes (Exos) aggravate GC development by facilitating M2 macrophage polarization and long non-coding RNA (lncRNA) HCG18 was highly expressed in GC. This study aimed to investigate whether the exosomal lncRNA HCG18 regulated the M2 macrophage polarization in GC and the possible mechanism. METHODS: The isolated GC cells (GCCs)-Exos were identified using transmission electron microscopy, Nanoparticle Tracking Analysis and Western blot. The GCCs-Exos function was verified by enzyme-linked immunosorbent assay and flow cytometry. Meanwhile, the exosomal lncRNA HCG18 function was determined using thein vitro assays. Furthermore, the underlying mechanism of the exosomal lncRNA HCG18 that regulated M2 macrophage polarization in GC was investigated using dual-luciferase reporter gene assay and RNA pull-down. RESULTS: After the validation of GCCs-Exos, the GCCs-Exos facilitated the M2 macrophage polarization. The in vitro assays confirmed that the exosomal lncRNA HCG18 positively regulated the M2 macrophage polarization. Mechanistically, lncRNA HCG18 bound to miR-875-3p, miR-875-3p bound to KLF4. Furthermore, GCCs-exosomal lncRNA HCG18 elevated the KLF4 expression by decreasing miR-875-3p in macrophages to facilitate M2 macrophage polarization, thus alleviating GC. The in vivo assays clarified that the GCCs-exosomal lncRNA HCG18 restrained the tumor growth of GC induced by M2 macrophages. CONCLUSION: GCCs-exosomal lncRNA HCG18 elevated KLF4 expression by decreasing miR-875-3p in macrophages to facilitate the M2 macrophage polarization.

Proteomic Profiling Identifies Kaposi's Sarcoma-Associated Herpesvirus (KSHV)-Encoded LANASIM-Associated Proteins in Hypoxia.

Hypoxia signaling is a key regulator in the development and progression of many types of human malignancies, including viral cancers. The latency-associated nuclear antigen (LANA), encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) during latency, is a multifunctional protein that plays an essential role in viral episome maintenance and lytic gene silencing for inducing tumorigenesis. Although our previous studies have shown that LANA contains a SUMO-interacting motif (LANASIM), and hypoxia reduces SUMOylated KAP1 association with LANASIM, the physiological proteomic network of LANASIM-associated cellular proteins in response to hypoxia is still unclear. In this study, we individually established cell lines stably expressing wild-type LANA (LANAWT) and its SIM-deleted mutant (LANAdSIM) and treated them with or without hypoxia, followed by coimmunoprecipitation and mass spectrometry analysis to systemically identify the hypoxia-responsive profile of LANASIM-associated cellular proteins. We found that in hypoxia, the number of cellular proteins associated with LANAWT instead of LANAdSIM was dramatically increased. Functional network analysis revealed that two major pathways, which included cytoskeleton organization and DNA/RNA binding and processing pathways, were significantly enriched for 28 LANASIM-associated proteins in response to hypoxia. HNRNPU was one of the proteins consistently identified that interacted with LANASIM in different proteomic screening systems and responded to hypoxia. This study provides a proteomic profile of LANASIM-associated proteins in hypoxia and facilitates our understanding of the role of the collaboration between viral infection and the hypoxia response in inducing viral persistence and tumorigenesis. IMPORTANCE Kaposi's sarcoma-associated herpesvirus (KSHV) has been reported to be involved in the regulation of host proteins in response to hypoxic stress. LANA, one of the key latent proteins, contains a SUMO-interacting motif (LANASIM) and reduces the association with SUMOylated KAP1 upon hypoxic treatment. However, the physiological systematic network of LANASIM-associated cellular proteins in hypoxia is still unclear. Here, we revealed two major pathways, which included cytoskeleton organization and DNA/RNA binding and processing pathways, that were significantly enriched for 28 LANASIM-associated proteins in hypoxia. This discovery not only provides a proteomic profile of LANASIM-associated proteins in hypoxia but also facilitates our understanding of the collaboration between viral infection and hypoxic stress in inducing viral persistence and tumorigenesis.

Effect of policosanol from insect wax on amyloid ß-peptide-induced toxicity in a transgenic Caenorhabditis elegans model of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD), an age-related neurodegenerative disorder and a serious public health concern, is mainly caused by ß-amyloid (Aß)-induced toxicity. Currently, a limited number of drugs are effective against AD, and only a few are used for its treatment. According to traditional Chinese medicine, white wax is mainly composed of policosanol, hexacosanol, and octacosanol. Policosanol has been shown to reduce lipid levels in blood and alleviate the symptoms associated with diabetic complications and neurodegenerative disorders, such as Parkinson's disease and AD. However, the efficacy of policosanol depends on the purity and composition of the preparation, and the therapeutic efficacy of policosanol derived from insect wax (PIW) in AD is unknown. METHODS: Here, we identified the main components of PIW and investigated the effects of PIW on Aß-induced toxicity and life-span in a transgenic Caenorhabditis elegans model of AD, CL4176. Furthermore, we estimated the expression of amyloid precursor-like protein (apl-1) and the genes involved in various pathways associated with longevity and alleviation of AD-related symptoms in PIW-fed CL4176. RESULTS: PIW mainly consists of tetracosanol, hexacosanol, octacosanol, and triacontanol; it could decrease the Aß-induced paralysis rate from 86.87 to 66.97% (P < 0.01) and extend the life-span from 6.2 d to 7.8 d (P < 0.001) in CL4176 worms. Furthermore, PIW downregulated apl-1, a gene known to be associated with the levels of Aß deposits in C. elegans. Additionally, our results showed that PIW modulated the expression of genes associated with longevity-related pathways such as heat shock response, anti-oxidative stress, and glutamine cysteine synthetase. CONCLUSION: Our findings suggest that PIW may be a potential therapeutic agent for the prevention and treatment of AD. However, its effects on murine models and patients with AD need to be explored further.

Anti-androgenetic alopecia effect of policosanol from Chinese wax by regulating abnormal hormone levels to suppress premature hair follicle entry into the regression phase.

Previously, we have demonstrated that policosanol from Chinese wax suppressed testosterone(T)-induced alopecia in mice. However, the underlying mechanism remained to be determined. Herein, we investigated the mechanism of policosanol against androgenetic alopecia (AGA). AGA was induced in Kunming mice by subcutaneous administration of testosterone propionate for 60 d. Policosanol (0.5 %, 1% or 2%) was applied topically on the back of mice. Finasteride (2%) was applied topically as a positive control. The serum T and estradiol (E2) concentrations were determined by ELISA after 28 and 60 days of treatment. The cutaneous expression or activity of key mediators of hair growth, such as alkaline phosphatase (ALP), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF), was measured. MTS assay was performed to evaluate cell proliferation in cultured human dermal papilla cells (DPCs) treated with dihydrotestosterone (DHT). Western blotting was performed to evaluate the protein expression of Bax, Bcl2, TGF-ß2, caspase-9, and caspase-3. We found lower T and T/E2 ratio in mice treated with policosanol than in the model group. Policosanol suppressed premature hair follicle entry into the regression phase, as shown by improving VEGF and EGF expression and ALP activity. The MTS assay showed that policosanol markedly inhibited the apoptosis of DHT-treated DPCs. Western blotting showed that policosanol significantly reduced the protein expression of TGF-ß2, cleaved caspese-9, cleaved caspase-3, and Bax, and increased that of Bcl2. The optimal effect was obtained with 12.50 g/mL policosanol. In conclusion, policosanol prevents androgenetic alopecia by regulating hormone levels and suppressing premature hair follicle entry into the regression phase.

Clinical outcome and operative cost comparison: Locked compression plate versus reconstruction plate in midshaft clavicle fractures.

OBJECTIVE: The aim of this study was to compare the clinical outcomes and operative cost of a locked compression plate (LCP) and a nonlocked reconstruction plate in the treatment of displaced midshaft clavicle fracture. METHODS: From January 2013 till March 2018, a total of 55 patients with acute unilateral closed midshaft clavicle fracture were treated with either a 3.5-mm pre-contoured LCP [32 patients; 25 men and 7 women; mean age: 35 years (range: 19-63 years)] or a 3.5-mm nonlocked reconstruction plate [23 patients; 20 men and 3 women; mean age: 31.4 years (range: 17-61 years)]. The clinical outcomes in terms of fracture union, Quick Disability of Arm, Shoulder and Hand (DASH) score, implant irritation, failure rate, and reoperation rate were evaluated retrospectively. The patient billing records were reviewed to obtain primary operation, reoperation, and total operative cost for midshaft clavicle fracture. These values were analyzed and converted from Malaysia Ringgit (RM) to United States Dollar (USD) at the exchange rate of RM 1 to USD 0.24. All patients were followed up for at least one-year duration. RESULTS: The mean time to fracture union, implant irritation, implant failure, and reoperation rate showed no significant difference between the two groups of patients. The mean Quick DASH score was significantly better in the reconstruction plate group with 13 points compared with 28 points in the LCP group (p=0.003). In terms of total operative cost, the LCP group recorded a cost of USD 391 higher than the reconstruction plate group (p<0.001). CONCLUSION: The 3.5-mm reconstruction plate achieved not only satisfactory clinical outcomes but was also more cost-effective than the LCP in the treatment of displaced midshaft clavicle fractures. LEVEL OF EVIDENCE: Level III, Therapeutic study.

Immunohistochemical basigin expression level in thyroid cancer tissues.

BACKGROUND: Thyroid cancer (TC) is the most common endocrine malignancy; basigin (also known as BSG) plays a crucial role in tumor cell invasion, metastasis, and angiogenesis. This study was designed to identify the change of BSG expression in TC and its possible potential mechanism. METHODS: The BSG expression levels in TC were demonstrated using data collected from in-house immunohistochemical (IHC), RNA-sequencing (RNA-seq), microarrays, and literatures. Integrated analysis was performed to determined BSG expression levels in TC comprehensively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed with the integration of BSG co-expressed genes and differentially expressed genes (DEGs) in TC tissues to explore the potential mechanisms of BSG in TC. RESULTS: The protein expression level of BSG was significantly higher in TC cases based on the IHC experiments. In addition, the combined SMD for BSG expression was 0.39 (p < 0.0001), the diagnostic odds ratio was 3.69, and the AUC of the sROC curve was 0.6986 using 1182 TC cases and 437 non-cancerous cases from 17 independent datasets. Furthermore, BSG co-expressed genes tended to be enriched in gene terms of the extracellular matrix (ECM), cell adhesion, and cell-cell interactions. The expression levels of nine hub BSG co-expressed genes were markedly upregulated in TC cases. CONCLUSION: BSG expression levels were closely correlated with the progression of TC and may affect the signals of the ECM, cell adhesion, and cell-cell interactions.

Novel Carbon Quantum Dots/Silver Blended Polysulfone Membrane with Improved Properties and Enhanced Performance in Tartrazine Dye Removal.

This study produced a novel polysulfone (PSF) membrane for dye removal using lemon-derived carbon quantum dots-grafted silver nanoparticles (Ag/CQDs) as membrane nanofiller. The preparation of CQDs was completed by undergoing hydrothermal treatment to carbonize the pulp-free lemon juice into CQD solution. The CQD solution was then coupled with Ag nanoparticles to form Ag/CQDs nanohybrid. The synthesized powders were characterized in terms of morphologies, functional groups and surface charges. A set of membranes was fabricated with different loadings of Ag/CQDs powder using the nonsolvent-induced phase separation (NIPS) method. The modified membranes were studied in terms of morphology, elemental composition, hydrophilicity and pore size. In addition, pure water flux, rejection test and fouling analysis of the membranes were evaluated using tartrazine dye. From the results, 0.5 wt % of Ag/CQD was identified as the optimum loading to be incorporated with the pristine PSF membrane. The modified membrane exhibited an excellent pure water permeability and dye rejection with improvements of 169% and 92%, respectively. In addition, the composite membrane also experienced lower flux decline, higher reversible fouling and lower irreversible fouling. This study has proven that the addition of CQD additives into membrane greatly improves the polymeric membrane's properties and filtration performance.