Tzu Chi Medical Journal最新文献

The most common STD that triggers cervical cancer is the human papillomavirus. More than 20 types of human papillomavirus (HPV) can induce uterine cervical cancer. Almost all women acquire genital HPV infection soon after their first intercourse, with most of them clearing the virus within 3 years. An immune response is necessary to clear. The first responders to HPV infection are the innate immune system elements composed of macrophages, keratinocytes, natural killer cells, and natural killer T-lymphocytic (NKT) cells. Cytotoxic T lymphocytes (CTLs) comprise the second line of defense and kill HPV16-infected cells expressing various peptides derived from their transforming early viral oncoproteins, mainly E2•E6. Even though HPV can manage to trick away our immune systems, first of all, it is important to emphasize that HPV replication does not kill the host cells. It does not replicate viral antigens or cause inflammation. The HPV16 E6 and E7 genes suppress host cell type 1 interferons (IFNs), which are detectable after infection. The patient may have immunological tolerance; hence, there are no costimulatory signals from inflammatory cytokines like IFNs during antigen recognition. Evidence shows that HlA class I generations have been inhibited by HPV16 E5, which could protect this tumor cell from CTL attack. HPV16 E7 is responsible for initiating immunotolerance and increasing regulatory T cells (Treg) to repress immunological regression. Evasion from immune system protection plays a critical role in the outcome of persistent HPV infection and the development of cervical cancer. Vaccination against HPV16 and 18 during adolescence is the most effective method for preventing cervical cancer in women, considering the immunological processes involved.

Objectives: The optimization of polyethylene glycol (PEG)-based extracellular vesicles (EVs) extraction from human follicular fluid (FF) and serum was investigated, and their functional analysis was confirmed. The PEG-based EV results were compared to the ExoQuick (ExoQ)-based EV.

Materials and methods: FF-EVs and serum-EVs were extracted by using different concentrations of PEG (8000). Nanoparticle tracking analysis was used to count the particles, and electron microscopy of EVs was performed for visualization. Exosomes were confirmed by the western blot analysis with exosome-specific markers. RNA and microRNA were extracted from exosomes and quantitative polymerase chain reaction analysis was performed. Fallopian tube epithelial (FTE) cells were used for the EV uptake experiment and an anchorage-independent growth test to confirm that extracted EVs harbor transformation activity.

Results: The PEG 8% enriched method produced the highest yield and the lowest carry-over protein. Salt containing PEG 8% produced a higher yield than nonsalted PEG 8%. Overnight enrichment increased four times and 18 times for PEG 8% and ExoQ-based EV extraction from FF. For serum EV, the same overnight enrichment moderately increased yield for both PEG 8% and ExoQ methods. Less carry-over protein resulted in more EV-promoted transformation activity.

Conclusion: This study overcomes the time-consuming, expensive, laborious, and complicated machine-dependent EV extraction methods. The study highlights that longer incubation time is needed for EV extraction from FF. PEG 8000-based EV extraction provided a higher yield and less carry-over protein than ExoQ-based EV extraction.

Objectives: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a challenging chronic inflammatory condition affecting the urinary bladder, with limited treatment options. This study aims to assess the clinical efficacy of repeated intravesical platelet-rich plasma (PRP) injections for promoting urothelial regeneration and reducing inflammation in patients with IC/BPS and investigate its correlation with subjective and objective treatment-related outcomes.

Materials and methods: Four monthly intravesical PRP injections were given to 98 patients with non-Hunner-type IC/BPS. Treatment outcomes were assessed using a global response assessment (GRA) score 3 months posttreatment. In addition, clinical symptom scores, pain severity, voiding diary data, uroflowmetry parameters, and GRA scores were compared before and after treatment and between different treatment outcome groups (satisfactory: GRA≥2 unsatisfactory: GRA<2). Baseline urine biomarkers were analyzed to identify potential treatment outcome predictors.

Results: After four PRP injections, 54 (55.1%) patients reported satisfactory outcomes. Lower urinary tract symptoms, bladder pain, urinary frequency, anxiety, and flow rate significantly improved from baseline (P < 0.05) in all patients, regardless of the treatment outcome. All patients experienced improved treatment outcomes and increased maximum bladder capacity with successive PRP treatments, and no major complications were reported. Urine biomarkers indicated elevated inflammation and oxidative stress biomarkers in patients with IC/BPS compared to controls.

Conclusion: Repeated PRP injections are safe and effective for reducing symptoms and bladder pain and improving bladder capacity in a majority of IC/BPS patients, with better outcomes observed in patients with a mild form of bladder inflammation. These results support PRP as a promising novel bladder therapy for IC/BPS.

Bladder outlet obstruction (BOO) is common in males with benign prostate enlargement (BPE) and often presents with different lower urinary tract symptoms. Overactive bladder (OAB) has been reported to be related to BOO, although it can also be idiopathic. The storage symptoms of BOO are often similar to those of OAB. The etiology and pathophysiology of both BPE and OAB are multifactorial with metabolic syndrome known as one of the factors. As of today, transurethral prostate surgery remains the gold standard for treating BOO associated with BPE. Intradetrusor onabotulinumtoxinA (BoNT-A) injections have been shown to be effective in treating OAB. However, they are usually administered after transurethral prostate surgery. In view of the strong therapeutic effects of both surgery and injections, the feasibility of combining them in one setting to increase patient comfort, convenience, and possibly results while decreasing costs is appealing to physicians. However, patient safety and possible complications have to be considered. In this article, we review available studies of concurrent intradetrusor BoNT-A injections during transurethral prostate surgery. Although there is no definitive evidence supporting the concurrent use of intradetrusor BoNT-A during transurethral prostate surgery, there are no reports of increased complications too. Further large-scale randomized controlled trials would be necessary to validate the feasibility of combining the treatments in one setting and observe for possible complications.

Objectives: Gastric cancer (GC) is one of the most malignant tumors. Mounting studies highlighted gastric cancer stem cells (GCSCs) were responsible for the failure of treatment due to recurrence and drug resistance of advanced GC. However, targeted therapy against GCSC for improving GC prognosis suffered from lack of suitable models and molecular targets in terms of personalized medicine. To address this issue, two patient-derived GC cell lines SD209 and SD292 with cancer stem cells (CSCs) such as phenotype were isolated for establishing targeted therapy aiming at critical metastatic signaling in GC.

Materials and methods: The primary patient-derived GCSCs were established from parts of GC tissues for characterization of stem cells (SCs) phenotype at both cellular and molecular levels. Western blot and Immunohistochemistry (IHC) were performed for identifying the deregulated signaling in GC tissue. Immunofluorescence was used for analyzing proliferating and SC markers in GCSC attached on fibroblast. Acridine orange and propidium iodide analyses were performed for the survival of GCSC in suspensions.

Results: In the culture environments of both SD209 and SD292, a lot of mesenchymal fibroblasts spread and crowd together on which a lot of cell clumps, suspected as GCSC, were firmly attached. In the IHC analysis, the GCSC stemness genes CD44 and Ep-CAM increased in tumor tissues of SD209, whereas Nanog-1 and octamer-binding transcription factor 3 (OCT-3) increased in that of SD292. By immunofluorescent analysis of a proliferation marker Ki67, the growth of SD209 and SD292 on mesenchymal fibroblasts was found to be reduced by dasatinib, the inhibitor of the Src kinase whose activity was upregulated in tumor tissues of both GCs. Dasatinib also suppressed the expression of Nanog-1 and OCT-3 in SD292 attached on mesenchymal fibroblasts.

Conclusion: This study may provide a base for targeted therapy against GCSCs/GCs progression in future preclinical/clinical settings.

A decrease in the levels of low-density lipoprotein receptors (LDLRs) leads to the accumulation of LDL cholesterol (LDL-C) in the bloodstream, resulting in hypercholesterolemia and atherosclerotic cardiovascular diseases. Increasing the expression level or inducing the activity of LDLR in hepatocytes can effectively control hypercholesterolemia. Proprotein convertase subtilisin/kexin type 9 (PCSK9) protein, primarily produced in the liver, promotes the degradation of LDLR. Inhibiting the expression and/or function of PCSK9 can increase the levels of LDLR on the surface of hepatocytes and promote LDL-C clearance from the plasma. Thus, targeting PCSK9 represents a new strategy for developing preventive and therapeutic interventions for hypercholesterolemia. Currently, monoclonal antibodies are used as PCSK9 inhibitors in clinical practice. However, the need for oral and affordable anti-PCSK9 medications limits the perspective of choosing PCSK9 inhibitors for clinical usage. Emerging research reports have demonstrated that natural phytochemicals have efficacy in maintaining cholesterol stability and regulating lipid metabolism. Developing novel natural phytochemical PCSK9 inhibitors can serve as a starting point for developing small-molecule drugs to reduce plasma LDL-C levels in patients. In this review, we summarize the current literature on the critical role of PCSK9 in controlling LDLR degradation and hypercholesterolemia, and we discuss the results of studies attempting to develop PCSK9 inhibitors, with an emphasis on the inhibitory effects of natural phytochemicals on PCSK9. Furthermore, we provide insight into the mechanisms of action by which the reported phytochemicals exert their potential PCSK9 inhibitory effects against hypercholesterolemia.

Inflammation and stem cell mobilization or homing play pivotal roles in tissue repair and regeneration. This review explores their intricate interplay, elucidating their collaborative role in maintaining tissue homeostasis and responding to injury or disease. While examining the fundamentals of stem cells, we detail the mechanisms underlying inflammation, including immune cell recruitment and inflammatory mediator release, highlighting their self-renewal and differentiation capabilities. Central to our exploration is the modulation of hematopoietic stem cell behavior by inflammatory cues, driving their mobilization from the bone marrow niche into circulation. Key cytokines, chemokines, growth factors, and autophagy, an intracellular catabolic mechanism involved in this process, are discussed alongside their clinical relevance. Furthermore, mesenchymal stem cell homing in response to inflammation contributes to tissue repair processes. In addition, we discuss stem cell resilience in the face of inflammatory challenges. Moreover, we examine the reciprocal influence of stem cells on the inflammatory milieu, shaping immune responses and tissue repair. We underscore the potential of targeting inflammation-induced stem cell mobilization for regenerative therapies through extensive literature analysis and clinical insights. By unraveling the complex interplay between inflammation and stem cells, this review advances our understanding of tissue repair mechanisms and offers promising avenues for clinical translation in regenerative medicine.

Radiotherapy (RT) is one of the primary treatment modalities in managing cancer patients. Recently, combined RT and immunotherapy (IT) (i.e., radio-IT [RIT]) have been aggressively investigated in managing cancer patients. However, several issues in conducting RIT are challenging, such as incorporating advanced irradiation techniques, predictive/prognostic biomarkers, and other treatment modalities. Several clinical efforts and novel biomarkers have been introduced and developed to solve these challenges. For example, stereotactic radiosurgery/stereotactic radiotherapy, stereotactic body radiotherapy/stereotactic ablative body radiotherapy, and FLASH-RT have been applied for delivering precise irradiation to lung and liver tumors in conjunction with IT. Besides, several novel IT agents and incorporations of other therapies, such as targeted and thermal therapies, have been further investigated. The present study reviewed the emerging challenges of RIT in modern oncology. We also evaluated clinical practice, bench research, and multimodality treatments. In addition to several clinically applicable biomarkers, we emphasize the roles of advanced irradiation techniques and epigenetic modification as predictive/prognostic biomarkers and potential therapeutic targets. For example, 6(m) A-based epigenetic agents demonstrate the potential to enhance the treatment effects of RIT. However, further prospective randomized trials should be conducted to confirm their roles.

Cardiovascular diseases (CVDs) are major contributors to illness and death globally. Body mass index (BMI) is a well-established prognostic factor on cardiovascular risk outcome. Numerous investigations have provided evidence for the existence of the obesity paradox after percutaneous coronary intervention (PCI). However, the association between BMI and the results following PCI has not been extensively investigated in Asian populations. The research aims to fill the current void in understanding by investigating the association between BMI and clinical consequences following PCI, with a particular focus on Asian individuals. A systematic search was conducted through PubMed, ScienceDirect, and Cochrane Library to identify studies examining the effect of BMI on clinical outcome after PCI in Asia. R Studio 4.3.2 software was used to carry out the analysis of the data. A total of 182,110 patients who had gone through PCI were found in the 5 included cohorts. A meta-analysis conducted on the subjects revealed that patients who were overweight (odds ratio [OR] = 0.60, 95% confidence interval [CI] [0.57, 0.63], P < 0.0001) had a lower risk of all-cause mortality compared to individuals with a healthy weight and patients with obesity (OR = 0.65, 95% CI [0.41, 1.05], P = 0.006) had a lower risk of all-cause mortality than healthy weight individuals. The study also found that overweight patients (OR = 0.60, 95% CI [0.39, 0.91], P = 0.02) had a lower risk of cardiac mortality. In addition, obese patients (OR = 0.41, 95% CI [0.19, 0.88], P = 0.02) had a lower risk of noncardiac mortality. However, the study found that there were no differences in major adverse cardiovascular event, myocardial infarction, and bleeding between all patient groups. This meta-analysis supports the presence of an obesity paradox after PCI in Asian populations. The obesity paradox was evident in all-cause mortality, cardiac mortality, and noncardiac mortality.

Currently, the second most commonly diagnosed cancer in the world is lung cancer, and 85% of cases are non-small cell lung cancer (NSCLC). With growing knowledge of oncogene drivers and cancer immunology, several novel therapeutics have emerged to improve the prognostic outcomes of NSCLC. However, treatment outcomes remain diverse, and an accurate tool to achieve precision medicine is an unmet need. Radiomics, a method of extracting medical imaging features, is promising for precision medicine. Among all radiomic tools, ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET)-based radiomics provides distinct information on glycolytic activity and heterogeneity. In this review, we collected relevant literature from PubMed and summarized the various applications of ¹⁸F-FDG PET-derived radiomics in improving the detection of metastasis, subtyping histopathologies, characterizing driver mutations, assessing treatment response, and evaluating survival outcomes of NSCLC. Furthermore, we reviewed the values of ¹⁸F-FDG PET-based deep learning. Finally, several challenges and caveats exist in the implementation of ¹⁸F-FDG PET-based radiomics for NSCLC. Implementing ¹⁸F-FDG PET-based radiomics in clinical practice is necessary to ensure reproducibility. Moreover, basic studies elucidating the underlying biological significance of ¹⁸F-FDG PET-based radiomics are lacking. Current inadequacies hamper immediate clinical adoption; however, radiomic studies are progressively addressing these issues. ¹⁸F-FDG PET-based radiomics remains an invaluable and indispensable aspect of precision medicine for NSCLC.