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1.
Cancer Lett ; 598: 217095, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38964728

ABSTRACT

Head and neck squamous cell carcinoma (HNSCC) constitutes a significant global cancer burden, given its high prevalence and associated mortality. Despite substantial progress in survival rates due to the enhanced multidisciplinary approach to treatment, these methods often lead to severe tissue damage, compromised function, and potential toxicity. Thus, there is an imperative need for novel, effective, and minimally damaging treatment modalities. Neoadjuvant treatment, an emerging therapeutic strategy, is designed to reduce tumor size and curtail distant metastasis prior to definitive intervention. Currently, neoadjuvant chemotherapy (NACT) has optimized the treatment approach for a subset of HNSCC patients, yet it has not produced a noticeable enhancement in overall survival (OS). In the contemporary cancer therapeutics landscape, immunotherapy is gaining traction at an accelerated pace. Notably, neoadjuvant immunotherapy (NAIT) has shown promising radiological and pathological responses, coupled with encouraging efficacy in several clinical trials. This potentially paves the way for a myriad of possibilities in treatment de-escalation of HNSCC, which warrants further exploration. This paper reviews the existing strategies and efficacies of neoadjuvant immune checkpoint inhibitors (ICIs), along with potential de-escalation strategies. Furthermore, the challenges encountered in the context of the de-escalation strategies of NAIT are explored. The aim is to inform future research directions that strive to improve the quality of life (QoL) for patients battling HNSCC.

2.
J Infect Public Health ; 17(7): 102443, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38838606

ABSTRACT

BACKGROUND: The burden of chronic liver disease (CLD) deaths attributable to the hepatitis B virus (HBV) and hepatitis C virus (HCV) remains unknown. Further research is required to elucidate the extent of this burden in the eventual elimination of these diseases. METHODS: Data on liver cancer, cirrhosis, and other CLD among 204 countries and territories between 1990 and 2019 was extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) published in 2019. The Bayesian age-period-cohort model was used to analyze the temporal trend and predict the disease burden by 2030. RESULTS: The number of HCV-related CLD deaths surpassed that of CLD deaths caused by HBV in 2019 (536833 deaths versus 523003 deaths) and is expected to be maintained until 2030 (689124 deaths versus 628824 deaths). East Asia had the highest burden of chronic HBV and HCV infections during the study period. In 2019, the largest age-standardized death rates (ASDR) of CLD deaths caused by HBV and HCV were mainly observed in Western Sub-Saharan Africa (18.75%) and Eastern Sub-Saharan Africa (16.42%), respectively. South Asia and East Asia are predicted to have the highest number of CLD deaths related to HCV and HBV by 2030. Eastern Europe and South Asia show the largest expected increase in disease burden caused by HCV or HBV between 2019 and 2030. No GBD region is projected to achieve the WHO target of a 65% reduction in mortality from chronic HBV and HCV infections by 2030. CONCLUSIONS: Although the mortality of CLD caused by HBV and HCV decreased in the last three decades (from 1990 to 2019), the number of deaths will continue to increase until 2030. Therefore, governments and international organizations need to strengthen the effectiveness of vaccines, screening, and treatment, especially in potential emerging hotspot regions.


Subject(s)
Global Health , Hepatitis B, Chronic , Hepatitis C, Chronic , Humans , Global Health/statistics & numerical data , Hepatitis C, Chronic/mortality , Hepatitis C, Chronic/epidemiology , Hepatitis B, Chronic/mortality , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/complications , Male , Female , Risk Factors , Middle Aged , Adult , Hepatitis B/mortality , Hepatitis B/epidemiology , Global Burden of Disease , Liver Diseases/mortality , Liver Diseases/epidemiology , Chronic Disease/epidemiology , Hepatitis C/mortality , Hepatitis C/epidemiology , Bayes Theorem , Aged
6.
J Biomech ; 166: 112057, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38520934

ABSTRACT

Enhanced external counterpulsation (EECP) is a treatment and rehabilitation approach for ischemic diseases, including coronary artery disease. Its therapeutic benefits are primarily attributed to the improved blood circulation achieved through sequential mechanical compression of the lower extremities. However, despite the crucial role that hemodynamic effects in the lower extremity arteries play in determining the effectiveness of EECP treatment, most studies have focused on the diastole phase and ignored the systolic phase. In the present study, a novel siphon model (SM) was developed to investigate the interdependence of several hemodynamic parameters, including pulse wave velocity, femoral flow rate, the operation pressure of cuffs, and the mean blood flow changes in the femoral artery throughout EECP therapy. To verify the accuracy of the SM, we coupled the predicted afterload in the lower extremity arteries during deflation using SM with the 0D-1D patient-specific model. Finally, the simulation results were compared with clinical measurements obtained during EECP therapy to verify the applicability and accuracy of the SM, as well as the coupling method. The precision and reliability of the previously developed personalized approach were further affirmed in this study. The average waveform similarity coefficient between the simulation results and the clinical measurements during the rest state exceeded 90%. This work has the potential to enhance our understanding of the hemodynamic mechanisms involved in EECP treatment and provide valuable insights for clinical decision-making.


Subject(s)
Counterpulsation , Pulse Wave Analysis , Humans , Reproducibility of Results , Hemodynamics , Lower Extremity , Counterpulsation/methods
7.
J Stomatol Oral Maxillofac Surg ; 125(3S): 101846, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38556167

ABSTRACT

Oral and maxillofacial tumors pose a significant clinical challenge due to their tendency to recur, despite advancements in surgical removal techniques. The jaw's intricate structure further complicates treatments and affects patient quality of life. Consequently, emphasis has shifted towards pharmacological interventions, to potentially reduce invasive surgical procedures. One promising approach targets BRAF mutations, specifically the common V600E mutation. BRAF, a critical protein kinase, regulates cell growth and differentiation via the RAS-RAF-MEK-ERK-MAP kinase pathway. A specific nucleotide change at position 1799, swapping Thymine (T) for Adenine (A), results in the V600E mutation, causing unchecked cell growth. This mutation is common in certain oral and maxillofacial tumors like ameloblastoma. A recent neoadjuvant therapy targeting BRAF, involving the use of dabrafenib and trametinib, has showcased a promising, safe, and effective strategy for organ preservation in the treatment of mandibular ameloblastoma. This convergence of molecular insights and targeted therapies holds the key to managing BRAF-mutated oral and maxillofacial tumors effectively, promising improved patient outcomes.


Subject(s)
Ameloblastoma , Mutation , Proto-Oncogene Proteins B-raf , Humans , Proto-Oncogene Proteins B-raf/genetics , Ameloblastoma/genetics , Ameloblastoma/therapy , Ameloblastoma/diagnosis , Imidazoles/therapeutic use , Oximes/therapeutic use , Pyridones/therapeutic use , Pyridones/administration & dosage , Pyrimidinones/therapeutic use , Antineoplastic Agents/therapeutic use , Mouth Neoplasms/therapy , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Neoadjuvant Therapy/methods , Molecular Targeted Therapy
8.
Transl Cancer Res ; 13(1): 173-190, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38410201

ABSTRACT

Background: With the development of messenger RNA (mRNA)-based therapeutics for malignant tumor, mRNA vaccines have shown considerable promise for tumor immunotherapy. Immunophenotypes can reflect the tumor microenvironment, which might have a significant influence on the effect of immunotherapy. This study seeks to discover and validate effective antigens that can be employed to develop mRNA vaccines for hepatocellular carcinoma (HCC) and to construct immunophenotypes and immune landscapes to identify potential beneficiaries. Methods: RNA sequencing (RNASeq) data, mutation information, and clinical information were obtained from HCC patients and control cases from The Cancer Genome Atlas - Liver Hepatocellular Carcinoma (TCGA-LIHC), International Cancer Genome Consortium - Liver Cancer (ICGC-LIRI) and Gene Expression Omnibus (GEO) cohorts. Gene Expression Profiling Interactive Analysis (GEPIA2.0), cBioPortal for Cancer Genomics (cBioPortal), Tumor IMmune Estimation Resource (TIMER2.0), and immunohistochemistry (IHC) were employed to discover tumor antigens. ConsensusClusterPlus was employed to perform consistency matrix building and immunophenotypic clustering. Single sample gene set enrichment analysis (ssGSEA), ESTIMATE and monocle2 were employed to map immune cell distribution. Weighted correlation network analysis (WGCNA) was employed to identify potential gene modules that influence the efficacy of mRNA vaccines. Results: Six antigen targets were discovered in the TCGA cohort, including AURKA, CDC25C, KPNA2, MCM3, NEK2 and TUBG1, which were associated with antigen-presenting cell infiltration and poor prognosis. IHC scores of AURKA, CDC25C and MCM3 were higher in tumor tissues, and high scores of AURKA and CDC25C indicated poor prognosis in the validation cohort. Five immunophenotypes derived from TCGA-LIHC and ICGC-LIRI cohorts were consistent. Furthermore, increased expression of blue and black modules may reduce vaccine responsiveness. Conclusions: AURKA, CDC25C, KPNA2, MCM3, NEK2 and TUBG1 may be potential targets for mRNA vaccine development for HCC, especially AURKA and CDC25C. HCC patients with IS1 and IS5 subtypes perhaps present an autoimmunosuppressed state, then IS2 and IS3 subtypes perhaps the potential beneficiaries.

9.
Cancer Lett ; 588: 216740, 2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38423247

ABSTRACT

Lymph node dissection has been a long-standing diagnostic and therapeutic strategy for metastatic cancers. However, questions over myriad related complications and survival outcomes are continuously debated. Immunotherapy, particularly neoadjuvant immunotherapy, has revolutionized the conventional paradigm of cancer treatment, yet has benefited only a fraction of patients. Emerging evidence has unveiled the role of lymph nodes as pivotal responders to immunotherapy, whose absence may contribute to drastic impairment in treatment efficacy, again posing challenges over excessive lymph node dissection. Hence, centering around this theme, we concentrate on the mechanisms of immune activation in lymph nodes and provide an overview of minimally invasive lymph node metastasis diagnosis, current best practices for activating lymph nodes, and the prognostic outcomes of omitting lymph node dissection. In particular, we discuss the potential for future comprehensive cancer treatment with effective activation of immunotherapy driven by lymph node preservation and highlight the challenges ahead to achieve this goal.


Subject(s)
Lymph Node Excision , Lymph Nodes , Humans , Lymph Nodes/pathology , Prognosis , Lymphatic Metastasis/pathology , Immunotherapy
10.
World J Urol ; 42(1): 14, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38189837

ABSTRACT

PURPOSE: Bladder neck contracture (BNC) is a rare but intolerant complication after transurethral surgery of prostate. The present study aims to investigate the incidence and risk factors of BNC in patients diagnosed benign prostate hyperplasia (BPH) and following transurethral resection or enucleation of the prostate (TURP/TUEP). METHODS: This retrospective study included 1008 BPH individuals who underwent transurethral surgery of the prostate between January 2017 and January 2022. Patients' demographics, medical comorbidities, urologic characteristics, perioperative parameters, and the presence of BNC were documented. Univariate and multivariate analyses were conducted to identify the risk factors. RESULTS: A total of 2% (20/1008) BPH patients developed BNC postoperatively and the median occurring time was 5.8 months. Particularly, the incidences of BNC were 4.7% and 1.3% in patients underwent Bipolar-TURP and TUEP respectively. Preoperative urinary tract infection (UTI), elevated PSA, smaller prostate volume (PV), bladder diverticulum (BD), and B-TURP were significantly associated with BNC in the univariate analysis. Further multivariate logistic regression demonstrated preoperative UTI (OR 4.04, 95% CI 2.25 to 17.42, p < 0.001), BD (OR 7.40, 95% CI 1.83 to 31.66, p < 0.001), and B-TURP (OR 3.97, 95% CI 1.55 to 10.18, p = 0.004) as independent risk factors. All BNC patients were treated with transurethral incision of the bladder neck (TUIBN) combined with local multisite injection of betamethasone. During a median follow-up of 35.8 months, 35% (7/20) of BNC patients recurred at a median time of 1.8 months. CONCLUSION: BNC was a low-frequency complication following transurethral surgery of prostate. Preoperative UTI, BD, and B-TURP were likely independent risk factors of BNC. TUIBN combined with local multisite injection of betamethasone may be promising choice for BNC treatment.


Subject(s)
Contracture , Prostatic Hyperplasia , Male , Humans , Urinary Bladder , Prostate , Retrospective Studies , Prostatic Hyperplasia/surgery , Contracture/epidemiology , Contracture/etiology , Betamethasone
11.
J Endourol ; 38(4): 340-346, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38243842

ABSTRACT

Background: The objective of this study was to explore the perioperative outcomes of single-plane posterior retroperitoneoscopic adrenalectomy (SPRA) guided by indocyanine green dye (ICG) fluorescence imaging. Methods: A retrospective analysis of patients who underwent SPRA from April to September 2023 in our center was conducted. Patients were divided into the ICG group and the non-ICG group, based on whether they received intraoperative ICG fluorescence guided or not. Baseline and perioperative data were recorded and analyzed by R software (R 4.3.1). Results: A total of 23 patients were enrolled in the study, with 12 in the ICG group and 11 in the non-ICG group. The demographics including age, gender, body mass index, or American Society of Anesthesiologists classification showed no significant differences between groups. There were obvious advantages in shortening adrenal gland localization time and total operative time, as well as reducing estimated blood loss in the ICG group compared with the non-ICG group (5.58 ± 0.36 minutes vs 7.55 ± 0.62 minutes, p < 0.001; 27.50 ± 5.46 minutes vs 45.00 ± 10.99 minutes, p < 0.001; 22.91 ± 7.57 mL vs 54.54 ± 18.90 mL, p < 0.001; respectively). Furthermore, patients in the ICG group exhibited significantly lower visual analog pain scale scores at 24 hours postoperatively and at discharge (p = 0.001 and p = 0.006, respectively). The oral intake intervals, hospital stays, and perioperative complications were comparable between groups. Conclusions: ICG-guided SPRA could be a safe and effective procedure for patients with adrenal tumors. This technique improves the accuracy and efficacy of adrenal gland localization and has shown benefits in perioperative outcomes. The use of ICG fluorescence guidance represents a promising clinical application.


Subject(s)
Adrenal Gland Neoplasms , Laparoscopy , Humans , Indocyanine Green , Adrenalectomy/methods , Retrospective Studies , Adrenal Gland Neoplasms/surgery , Length of Stay , Laparoscopy/methods
12.
Geroscience ; 46(3): 3361-3375, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38270807

ABSTRACT

Bladder cancer (BCa) incidence is tightly linked to aging. Older patients with BCa present with higher grade tumors and have worse outcomes on Bacillus-Calmette-Guerin (BCG) immunotherapy. Aging is also known to result in changes in the gut microbiome over mammalian lifespan, with recent studies linking alterations in the gut microbiome to changes in tumor immunity. There is limited information on the microbiome in BCa models though, despite known links to aging and immunotherapy. The purpose of this study was to evaluate how aging impacts tumor formation, inflammation, and the microbiome of mice given the model BCa carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). We hypothesized old animals would have larger, more inflamed tumors and a shift in their fecal microbiome compared to their younger counterparts. Young (~8-week-old) or old (~78-week-old) C57Bl/6J animals were administered 0.05% BBN in drinking water for 16 weeks and then euthanized or allowed to progress for an additional 4 weeks. After 16 weeks of BBN, old mice had higher bladder to body weight ratio than young mice, and also muscle invasive tumors, which were not seen in their young counterparts. Old animals also had increased innate immune recruitment, but CD4+/CD8+ T cell recruitment did not appear different. BBN dramatically altered the microbiome in both sets of animals as measured by ß-diversity, including changes in multiple genera of bacteria. These data suggest old mice have a differential response to BBN-induced BCa. Given the median age of patients with BCa, understanding how the aged phenotype interacts with BCa is imperative.


Subject(s)
Butylhydroxybutylnitrosamine , Urinary Bladder Neoplasms , Humans , Mice , Animals , Aged , Disease Models, Animal , Butylhydroxybutylnitrosamine/toxicity , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Carcinogens , Aging , Mammals
13.
Phys Chem Chem Phys ; 25(28): 19082-19090, 2023 Jul 19.
Article in English | MEDLINE | ID: mdl-37427572

ABSTRACT

By using density functional theory calculations combined with the nonequilibrium Green's function method and machine learning, we systematically studied the thermoelectric properties of four kinds of porous graphene nanosheets (PGNS) before and after nitrogen doping. The results show that the thermoelectric performance of porous graphene nanosheets along the armchair or zigzag chiral direction is improved due to the dramatically enhanced power factor caused by nitrogen doping. The calculated ZT values of nitrogen-doped porous graphene nanosheets are boosted by about one order of magnitude compared with those of undoped porous graphene nanosheets at room temperature. More importantly, an anisotropic thermoelectric transport is found in the nitrogen-doped porous graphene nanosheets. The results show that the ZT values of nitrogen-doped porous graphene nanosheets along the zigzag transport direction are nearly 11 times larger than those of them along the armchair transport direction. These results reveal that the thermoelectric properties of porous graphene nanosheets can be well regulated by nitrogen doping, and provide a good theoretical guidance for their application in thermoelectric devices.

14.
Children (Basel) ; 10(7)2023 Jun 28.
Article in English | MEDLINE | ID: mdl-37508616

ABSTRACT

Individuals with specific language impairment (SLI) struggle with language acquisition despite average non-verbal intelligence and otherwise typical development. One SLI account focuses on grammar acquisition delay. The current study aimed to detect novel rare genetic variants associated with performance on a grammar assessment, the Test of Early Grammatical Impairment (TEGI), in English-speaking children. The TEGI was selected due to its sensitivity and specificity, consistently high heritability estimates, and its absence from all but one molecular genetic study. We performed whole exome sequencing (WES) in eight families with SLI (n = 74 total) and follow-up Sanger sequencing in additional unrelated probands (n = 146). We prioritized rare exonic variants shared by individuals with low TEGI performance (n = 34) from at least two families under two filtering workflows: (1) novel and (2) previously reported candidate genes. Candidate variants were observed on six new genes (PDHA2, PCDHB3, FURIN, NOL6, IQGAP3, and BAHCC1), and two genes previously reported for overall language ability (GLI3 and FLNB). We specifically suggest PCDHB3, a protocadherin gene, and NOL6 are critical for ribosome synthesis, as they are important targets of SLI investigation. The proposed SLI candidate genes associated with TEGI performance emphasize the utility of precise phenotyping and family-based genetic study.

15.
Int J Med Sci ; 20(7): 836-848, 2023.
Article in English | MEDLINE | ID: mdl-37324184

ABSTRACT

Atherosclerosis is a chronic, inflammatory disease characterized by a lipid-driven infiltration of inflammatory cells in large and medium arteries and is considered to be a major underlying cause of cardiovascular diseases. Cuproptosis, a novel form of cell death, is highly linked to mitochondrial metabolism and mediated by protein lipoylation. However, the clinical implication of cuproptosis-related genes (CRGs) in atherosclerosis remains unclear. In this study, genes collected from the GEO database intersected with CRGs were identified in atherosclerosis. GSEA, GO and KEGG pathway enrichment analyses were performed for functional annotation. Through the random forest algorithm and the construction of a protein-protein interaction (PPI) network, eight selected genes (LOXL2, SLC31A1, ATP7A, SLC31A2, COA6, UBE2D1, CP and SOD1) and a vital cuproptosis-related gene FDX1 were then further validated. Two independent datasets (GSE28829 (N = 29), GSE100927 (N = 104)) were collected to construct the signature of CRGs for validation in atherosclerosis. Consistently, the atherosclerosis plaques showed significantly higher expression of SLC31A1, SLC31A2 and lower expression of SOD1 than the normal intimae. The area under the curve (AUC) of SLC31A1, SLC31A2 and SOD1 performed well for the diagnostic validation in the two datasets. In conclusion, the cuproptosis-related gene signature could serve as a potential diagnostic biomarker for atherosclerosis and may offer novel insights into the treatment of cardiovascular diseases. Based on the hub genes, a competing endogenous RNA (ceRNA) network of lncRNA-miRNA-mRNA and a transcription factor regulation network were ultimately constructed to explore the possible regulatory mechanism in atherosclerosis.


Subject(s)
Apoptosis , Atherosclerosis , Cardiovascular Diseases , Plaque, Atherosclerotic , Humans , Atherosclerosis/diagnosis , Atherosclerosis/genetics , Biomarkers , Carrier Proteins , Mitochondrial Proteins , Superoxide Dismutase-1 , Copper
16.
ACS Nano ; 17(12): 11593-11606, 2023 06 27.
Article in English | MEDLINE | ID: mdl-37306553

ABSTRACT

Present day strategies for delivery of wireless photodynamic therapy (PDT) to deep-seated targets are limited by the inadequacy of irradiance and insufficient therapeutic depth. Here we report the design and preclinical validation of a flexible wireless upconversion nanoparticle (UCNP) implant (SIRIUS) that is capable of large field, high intensity illumination for PDT of deep-seated tumors. The implant achieves this by incorporating submicrometer core-shell-shell NaYF4 UCNPs into its design, which significantly enhances upconversion efficiency and mitigates light loss from surface quenching. We demonstrate the efficacy of SIRIUS UCNP implant mediated PDT in preclinical breast cancer disease models. In our in vitro experiments, SIRIUS directed 5-Aminolevulinic Acid (5-ALA) based wireless PDT leads to significant reactive oxygen species (ROS) generation and tumor apoptosis in hormonal receptor+/HER2+ (MCF7) and triple-negative (MDA-MB-231) breast cancer cell lines. In our in vivo rodent model, SIRIUS-driven PDT is shown to be significant in regressing tumors when applied to orthotopically inoculated breast tumors. Following successful preclinical validation, we also describe a clinical prototype of UCNP breast implant with potential dual cosmetic and onco-therapeutic functions. SIRIUS is an upconversion breast implant for wireless PDT that fulfils all the design prerequisites necessary for seamless clinical translation.


Subject(s)
Breast Implants , Nanoparticles , Photochemotherapy , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Aminolevulinic Acid , Cell Line, Tumor
17.
Biomater Sci ; 11(13): 4557-4573, 2023 Jun 27.
Article in English | MEDLINE | ID: mdl-37159255

ABSTRACT

Chondroitin sulfate (CS), a glycosaminoglycan of native cartilage, has shown its potential in promoting chondrogenesis of mesenchymal stem cells (MSCs), whereas the effect of matrix stiffness in a CS-containing 3D environment on chondrogenesis is still poorly understood. Herein, this study aimed at assessing the effect of CS concentration and stiffness of CS-containing hydrogels on the chondrogenesis of MSCs. Hydrogels composed of 6% (w/v) gelatin methacryloyl (GelMA) and three concentrations, i.e., 4%, 6%, or 10% (w/v), of methacrylated chondroitin sulfate (CSMA) were prepared. The hydrogels of each composition were prepared with two stiffness values (33.36 ± 8.25 kPa vs. 8.42 ± 2.83 kPa). Physical characterization showed similar microporous structures among the six groups, higher swelling ratios and faster degradation in the soft hydrogel groups. MSCs were encapsulated in the six groups of hydrogels and they underwent 28-day chondrogenic differentiation. The cell viability in each group on day 1 was similar and most cells exhibited a round shape without spreading. Afterwards, cellular protrusions in soft hydrogels remained filopodium-like from day 14 to day 28, while most protrusions were lamellipodium-like in stiff hydrogels on day 14 and then transformed into a spherical shape on day 28. The expression of chondrogenic markers analysed by real-time qPCR and immunohistochemical staining demonstrated that the optimal CS concentration for chondrogenesis was 6% (w/v) regardless of the stiffness of hydrogels. In addition, with the same CSMA concentration, the trend was observed that the stiff hydrogels supported superior chondrogenesis of MSCs compared to the soft hydrogel. To summarize, this study presents an advancement in the optimization of CSMA concentration and stiffness of hydrogels for chondrogenesis. In the CSMA/GelMA hydrogel, 6% (w/v) CSMA with an initial Young's modulus around 33 kPa was recommended for cartilage tissue engineering.


Subject(s)
Chondroitin Sulfates , Mesenchymal Stem Cells , Chondroitin Sulfates/pharmacology , Chondrogenesis , Cell Differentiation , Cells, Cultured , Hydrogels/chemistry
18.
Front Microbiol ; 14: 1133782, 2023.
Article in English | MEDLINE | ID: mdl-37089532

ABSTRACT

Objective: Increasing evidence suggests that gut microbiota is involved in the occurrence and progression of urinary system diseases such as clear cell renal cell carcinoma (ccRCC). However, the mechanism of how alteration of gut metagenome promotes ccRCC remains unclear. Here we aim to elucidate the association of specific gut bacteria and their metabolites with ccRCC. Methods: In a pilot case-control study among 30 ccRCC patients (RCC group) and 30 healthy controls (Control group), 16S ribosomal RNA (rRNA) gene sequencing were analyzed from fecal samples collected prior to surgery or hospitalization. Alpha diversity and beta diversity analysis of the gut microbiota were performed, and differential taxa were identified by multivariate statistics. Meanwhile, serum metabolism was measured by UHPLC-MS, and differential genes were identified based on the TCGA database. Results: Alpha diversity found there were no significant microbial diversity differences of gut microbiota between the RCC group and the Control group. However, beta diversity analysis showed that the overall structures of the two groups were significantly separated (p = 0.008). Random Forests revealed the relative abundances of 20 species differed significantly between the RCC group and the Control group, among which nine species were enriched in the RCC group such as Desulfovibrionaceae, and 11 species were less abundant such as four kinds of Lactobacillus. Concomitantly, serum level of taurine, which was considered to be consumed by Desulfovibrionaceae and released by Lactobacillus, has decreased in the RCC group. In addition, macrophage-related genes such as Gabbr1 was upregulated in ccRCC patients. Conclusion: Reduction of protective bacteria, proliferation of sulfide-degrading bacteria Desulfovibrionaceae, reduction of taurine, and enrichment of macrophage related genes might be the risk predictors of ccRCC.

19.
Nat Prod Res ; 37(14): 2359-2366, 2023 Jul.
Article in English | MEDLINE | ID: mdl-35220846

ABSTRACT

Two new cycloartanes, combretic acid C (1) and combretanone I (3), were isolated from the leaves of Combretum quadrangulare Kurz, together with the previously-reported combretic acids A-B (2 and 5) and combretanone A (4). An extensive set of spectroscopic methods were used to elucidate the structures of these compounds. Cytotoxicity against the K562 cancer cell line was evaluated. Compound 1 showed strong activity, with an IC50 value of 9.7 µM. The other compounds showed moderate activity. Alpha-glucosidase inhibition was also evaluated. The isolated compounds showed moderate inhibition, with IC50 values in the range 102.2-194.7 µM.


Subject(s)
Combretum , Triterpenes , Combretum/chemistry , Vietnam , Triterpenes/chemistry , Plant Leaves/chemistry
20.
Transl Androl Urol ; 11(8): 1130-1147, 2022 Aug.
Article in English | MEDLINE | ID: mdl-36092848

ABSTRACT

Background: Ferroptosis-related genes (FRGs) play vital roles in survival and prognosis of prostate cancer (PCa) patients. We establish a ferroptosis-related prediction model through bioinformatics analysis for overall survival (OS) and disease-free survival (DFS), so as to evaluate the clinical survival status through the characteristics of immune cell infiltration (ICI), which could provide information for treatment monitoring. Methods: At first, 268 FRGs were obtained from previous studies. Differentially expressed FRGs were identified based on The Cancer Genome Atlas (TCGA) database, and FRG enrichment analysis was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We then performed univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses to establish OS- and DFS-related prognostic prediction models. The association of the model and clinicopathological features was further analyzed. Subsequently, unique genomic signatures of immune cell subsets were obtained through the KEGG database. Based on specific genes associated with ferroptosis and their association with ICI, immune infiltration was assessed in patients in different risk groups. Results: We constructed an OS- and an DFS-prognostic model through bioinformatics analysis. The predicted values of OS and DFS-related models were higher in T3-4 than in T1-2 (P=0.0057, P<0.001), and the predicted value of the DFS model in N0 stage was higher than that in N1 stage (P=0.0136). Results of Single-sample gene set enrichment analysis (ssGSEA) on the basis of the KEGG dataset showed p53 signaling being the most enriched signal in the high-risk group, while endocytosis was the most enriched signal in the low-risk group. M2 macrophages (P=0.007) and neutrophils (P=0.024) were enriched in the high-risk group, and CD4-activated memory T cells were significantly accumulated in the low-risk group (P=0.017). Conclusions: The OS- and DFS-related model based on FRGs and ICI create new insights into the disease state assessment of PCa patients., which may aid in the development of individualized and precise treatment in the future.

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