Treatment Strategies Research Articles

Glucose transporters in lymphocytes: expression and effects on lymphocyte functions

Glucose uptake by lymphocytes is dependent on the facilitative glucose transporters (GLUT1, GLUT3, GLUT4, and GLUT6) of the GLUT family and the Na+-coupled glucose transporter SGLT1. GLUTs and SGLTs are widely expressed in mammals, and their expression and functions may affect cell development, homeostasis, activation, and differentiation. This article details the important functions of several GLUTs and SGLTs in lymphocytes and points out that glucose transporters play a key role in supplying energy for lymphocytes, maintaining intracellular glucose homeostasis, and improving the efficiency of immune responses, which reflect their key roles in signal transduction. Probing into the effects of glucose transporters on lymphocyte functions will help to decipher the functioning mechanisms of lymphocytes in diseases. Furthermore, this paper prospects the application values of glucose transporters in lymphocytes from molecular biology, aiming to provide better strategies for the clinical treatment of lymphocyte-related diseases and promote the research and development of targeted therapeutic drugs.

Significance and treatment strategies of pathologic complete response after neoadjuvant therapy for gastric cancer

Neoadjuvant therapy, as an important part of comprehensive treatment for locally advanced gastric cancer, has been recommended by various guidelines. Partial locally advanced gastric cancer patients can achieve pathologic complete response (pCR) after neoadjuvant therapy, thus achieving relatively good prognosis. However, there is still controversy over whether complete remission in local pathology can translate into survival benefits, whether pCR is equivalent to cure, and whether subsequent adjuvant therapy is needed. Therefore, how to predict patients who can achieve pathologic complete response after neoadjuvant therapy and identify truly cured patients is the direction of future exploration.

Histologic subtypes of non-muscle invasive bladder cancer

The majority of bladder cancers (BCs) are non-muscle invasive BCs (NMIBCs) and show the morphology of a conventional urothelial carcinoma (UC). Aberrant morphology is rare but can be observed. The classification and characterization of histologic subtypes (HS) in UC in BC have mainly been described in muscle invasive bladder cancer (MIBC). However, the currently used classification is applied for invasive urothelial neoplasm and therefore, also valid for a subset of NMIBC. The standard transurethral diagnostic work-up misses the presence of HS in NMIBC in a considerable percentage of patients and the real prevalence is not known. HS in NMIBC are associated with an aggressive phenotype. Consequently, clinical guidelines categorize HS of NMIBC as ”(very) high-risk” tumors and recommend offering radical cystectomy to these patients. Alternative strategies for bladder preservation can only be offered to highly selected patients and ideally within clinical trials. Novel treatment strategies and biomarkers have been established MIBC and NMIBC but have not been comprehensively investigated in the context of HS in NMIBC. Further evaluation prior to implementation into clinical practice is needed.

Research progress and clinical strategies of medical treatment for chronic heart failure patients with reduced ejection fraction

Research progress and clinical strategies of medical treatment for chronic heart failure patients with reduced ejection fraction

Piezoelectric Analgesia Blocks Cancer-Induced Bone Pain.

The manipulation of cell surface receptors' activity will open a new frontier for drug development and disease treatment. However, limited by the desensitization of drugs, effective physical intervention strategy remains challenging. Here, the controllable internalization of transient receptor potential vanilloid 1 (TRPV1) on neural cells by local piezoelectric field is reported. Single-cell-level local electric field is construct by synthesizing piezoelectric BiOIO3 nanosheets (BIONSs). Upon a mild ultrasound of 0.08Wcm-2, an electric field of 15.29µV is generated on the surface of BIONSs, further inducing TRPV1 internalization in 5min. The as-downregulated TRPV1 expression results in the reduction of Ca2+ signal in a spinal neuron and the inhibition of the activity of wide range dynamic neurons, therefore effectively preventing the transmission of cancer-induced bone pain (CIBP). This strategy not only charts a new course for CIBP alleviation, but also introduces a promising nanotechnology for regulating cell surface receptors, showing significant potential in neuropathological and receptor-related diseases.

Genetic and clinical characteristics of single and compound types of patients with long QT syndrome type 3

Objective: To explore the genetic background and clinical features of patients with long QT syndrome type 3 (LQT3). Methods: This retrospective cohort included patients diagnosed with LQT3 at the Department of Cardiology, Renmin Hospital of Wuhan University from January 1998 to December 2022. Patients were categorized into compound type group and single type group based on the presence of a single SCN5A mutation. The two groups were followed up and the differences in baseline characteristics, electrocardiograms, and clinical events between the two groups and probands were compared. Kaplan-Meier curves were used for survival analysis, and the log-rank test was employed to compare the event-free survival rates of first cardiac events between the groups and probands. Results: A total of 97 LQT3 patients were enrolled, including 59 probands. The age at diagnosis was (23.45±19.86) years, with 46 patients (47.4%) being male. Among them, 89 patients were classified as single type group, while 8 patients were classified as compound type group. Genetic testing identified 49 SCN5A mutations, with missense mutations being the majority (91.8%), primarily located in transmembrane regions (40.8%, n=20), interdomain linker regions (28.6%, n=14), and C-terminus (22.4%, n=11). The first cardiac event occurred in 44 patients (45.4%), with an onset age of (13.82±12.50) years. The main trigger was identified as rest or sleep (54.5%, n=24). Compared with patients in single type group, patients in compound type group were younger at diagnosis ((10.35±10.28) years vs. (24.63±20.13) years, P=0.040), had a significantly higher proportion of syncope (87.5% (7/8) vs. 33.7% (30/89), P=0.009), aborted cardiac arrest (62.5% (5/8) vs. 11.2% (10/89), P=0.001), and a lower incidence of event-free survival rates of first cardiac events (12.5% (1/8) vs.58.4% (52/89), log-rank P=0.001). The probands in compound type group had a significantly higher proportion of aborted cardiac arrest comparing to probands in single type group (62.5% (5/8) vs. 17.6% (9/51), P=0.020), while the difference in the incidence rate of event-free survival rates of first cardiac events between the probands in two groups was not statistically significant (12.5% (1/8) vs. 39.2% (20/51), log-rank P=0.08). Conclusion: Compound type LQT3 patients are not uncommon. Such patients are diagnosed at a younger age and exhibit more severe phenotypes, requiring close follow-up and proactive intervention strategies.

Smart nanocarriers for enzyme-activated prodrug therapy.

Exogenous enzyme-activated prodrug therapy (EPT) is a potential cancer treatment strategy that delivers non-human enzymes into or on the surface of the cell and subsequently converts a non-toxic prodrug into an active cytotoxic substance at a specific location and time. The development of several pharmacological pairs based on EPT has been the focus of anticancer research for more than three decades. Numerous of these pharmacological pairs have progressed to clinical trials, and a few have achieved application in specific cancer therapies. The current review highlights the potential of enzyme-activated prodrug therapy as a promising anticancer treatment. Different microbial, plant, or viral enzymes and their corresponding prodrugs that advanced to clinical trials have been listed. Additionally, we discuss new trends in the field of enzyme-activated prodrug nanocarriers, including nanobubbles combined with ultrasound (NB/US), mesoscopic-sized polyion complex vesicles (PICsomes), nanoparticles, and extracellular vesicles (EVs), with special emphasis on smart stimuli-triggered drug release, hybrid nanocarriers, and the main application of nanotechnology in improving prodrugs.

Exploring the landscape of urinary tract melanomas: A review for pathologists and clinicians.

Melanomas originating within the urinary tract represent a rare and clinically challenging subset of malignancies. Despite extensive research on cutaneous melanomas, urinary tract melanomas remain relatively unexplored, presenting diagnostic dilemmas and limited treatment consensus. In this comprehensive review, we synthesize current knowledge on the epidemiology, risk factors, clinical presentation, histopathological characteristics, and treatment strategies specific to this disease. Enhancing clinical awareness, refining diagnostic approaches, and exploring novel therapeutic interventions hold promise for improving outcomes in this challenging malignancy subset.

Dutch multidisciplinary guideline on anterior knee pain: Patellofemoral pain and patellar tendinopathy.

The purpose of this study was to develop a multidisciplinary guideline for patellofemoral pain (PFP) and patellar tendinopathy (PT) to facilitate clinical decision-making in primary and secondary care. A multidisciplinary expert panel identified questions in clinical decision-making. Based on a systematic literature search, the strength of the scientific evidence was determined according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method and the weight assigned to the considerations by the expert panel together determined the strength of the recommendations. After confirming PFP or PT as a clinical diagnosis, patients should start with exercise therapy. Additional conservative treatments are indicated only when exercise therapy does not result in clinically relevant changes after six (PFP) or 12 (PT) weeks. Pain medications should be reserved for cases of severe pain. The additional value of imaging assessments for PT is limited. Open surgery is reserved for very specific cases of nonresponders to exercise therapy and those requiring additional conservative treatments. Although the certainty of evidence regarding exercise therapy for PFP and PT had to be downgraded ('very low GRADE' and 'low GRADE'), the expert panel advocates its use as the primary treatment strategy. The panel further formulated weaker recommendations regarding additional conservative treatments, pain medications, imaging assessments and open surgery ('very low GRADE' to 'low GRADE' assessment or absence of scientific evidence). This guideline recommends starting with exercise therapy for PFP and PT. The recommendations facilitate clinical decision-making, and thereby optimizing treatment and preventing unnecessary burdens, risks and costs to patients and society. Level V, clinical practice guideline.

Trends in HIV/AIDS-Related Mortality and the Impact of Antiretroviral Treatment Strategies in Lu'an City: A Comprehensive Analysis.

BACKGROUND There are many factors that affect human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)-related deaths, and different antiretroviral therapy (ART) strategies may affect HIV/AIDS-related fatality rates. However, studies on this area are very limited. This study aimed to evaluate the factors associated with HIV/AIDS-related mortality and the impact of different ART strategies in Lu'an City, Anhui Province, China, 1999-2023. MATERIAL AND METHODS Data of HIV/AIDS cases were downloaded from the China HIV/AIDS Comprehensive Response Information Management System, and were assessed to evaluate the impact of different ART strategies on the related fatality rate using interrupted time series (ITS). RESULTS We found that age at diagnosis of 15 years, 25 years, 40 years, and 60 years, as well as receiving ART, were protective factors against death (with P below 0.05), while lower CD4 count at the last CD4 count and the year of diagnosis before 2007 and between 2007 and 2016 were risk factors (with P below 0.05). ITS analysis revealed that in the year of the introduction of free ART in 2006, the fatality rate decreased by 38.60% (P=0.015). The fatality rate trend from 2006 to 2015 was -1.1%, which was not statistically significant (P=0.434). The fatality rate trend from 2016 to 2023 was -0.33%, indicating a decreasing trend (P=0.000). CONCLUSIONS Children under 15 years old and elderly patients had a higher risk of death. The main reasons for the decrease in HIV/AIDS-related fatality rate were ART, especially the "early treatment" strategy.

Emerging therapeutic strategies targeting bone signaling pathways in periodontitis.

Periodontitis is a multifactorial immune-mediated disease exacerbated by dysregulated alveolar bone homeostasis. Timely intervention is crucial for disease management to prevent tooth loss. To successfully manage periodontitis, it is imperative to understand the cellular and molecular mechanisms involved in its pathogenesis to develop novel treatment modalities. Non-surgical periodontal therapy (NSPT) such as subgingival instrumentation/debridement has been the underlying treatment strategy over the past decades. However, new NSPT approaches that target key signaling pathways regulating alveolar bone homeostasis have shown positive clinical outcomes. This narrative review aims to discuss endogenous bone homeostasis mechanisms impaired in periodontitis and highlight the clinical outcomes of preventive periodontal therapy to avoid invasive periodontal therapies. Although the anti-resorptive therapeutic adjuncts have demonstrated beneficial outcomes, adverse events have been reported. Diverse immunomodulatory therapies targeting the osteoblast/osteoclast (OB/OC) axis have shown promising outcomes invivo. Future controlled randomized clinical trials (RCT) would help clinicians and patients in the selection of novel preventing therapies targeting key molecules to effectively treat or prevent periodontitis.

Treatment patterns and healthcare resource utilization among patients with alopecia areata: A real-world chart review in South Korea.

Alopecia areata (AA) is a clinically heterogeneous, immune-mediated, non-scarring hair loss disorder. This real-world chart review sought to characterize treatment patterns and healthcare resource use among patients with severe AA in South Korea. A web-based chart review of 40 dermatologists was conducted in which the medical charts of 151 adult patients diagnosed with severe AA between May 2019 and April 2021 were reviewed. Anonymized data on patient characteristics, treatment patterns, healthcare resource use, and clinical outcomes were extracted from the date of severe disease diagnosis until the date of data collection (September-November 2022). Sixty-six percent of patients were diagnosed with severe disease at initial presentation, while 34% were re-classed to severe during the disease course. Mean estimated patient age at the time of diagnosis of severe AA was 37.1 (range 22-68) years. Fifty-three percent of patients were male. Most patients (93.4%) received pharmacological treatment for their condition; 45.5% received ≥2 lines of treatment with a mean duration of 24 months. First-line treatment discontinuation due to lack of efficacy occurred in 46.0% of cases. Hair regrowth occurred in 71.0% of patients, 59.2% of whom experienced major regrowth (≥60%) during the follow-up period. Median (95% confidence interval) time to regrowth was 13.7 (11.0-20.6) months. Treatment visit rates per person-year ranged from two (phototherapy) to 10 (topical treatment), dermatologist visits occurred at a rate of 12.9 per person-year and 6.0% of patients were hospitalized due to alopecia areata. The majority of hospitalizations were related to treatment and occurred in patients who received pulse systemic corticosteroid therapy. The patient and economic burden of AA in South Korea is high and there remains a critical unmet need among patients with severe AA with respect to the effectiveness of commonly used treatment strategies.

Gastric cancer in pregnancy: a review.

Malignant tumors including gastric cancer (GC) are the leading cause of deaths among reproductive women. Physiological morning sickness can mask the clinical manifestations of GC, whereas the clinical presence of metastatic tumors in the abdominal cavity may be easily mistaken for abdominal swelling caused by fetal growth. Pregnancy and delivery processes in young females could accelerate the growth of GC, leading to its rapid development and grave prognosis. Therefore, early diagnosis is critical and gastrointestinal endoscopy is recommended for any suspected pregnant woman with long-term morning sickness. Treatment strategies, including chemotherapy, resection surgery and radiotherapy, will be determined based on a comprehensive consideration of the status of both the fetus and the mother. Rational management, especially clinical multidisciplinary collaboration may significantly benefit such patients.

Perovskite-structured ultrasensitive CaMnO3 nanoenzyme enables highly efficient ultrasound-amplified and catalysis-involved synergistic tumor therapy

Catalytic nanoenzyme-mediated therapy with reactive oxygen species generation feature and tumor microenvironment regulation characteristic has demonstrated high therapeutic efficacy in oncological field, whereas its low enzyme-mimicking reaction efficacy typically results in dissatisfied therapeutic effect and outcome. Herein, an ultrasensitive CaMnO3 (CMO) nanoenzyme has been rationally designed and engineered for enzyodynamic-calcium overload synergistic tumor therapy. CMO nanoenzyme with oxidase (OXD)-, peroxidase (POD)- and glutathione peroxidase (GPx)-mimic activities is responsible for the generation of reactive oxygen species, the consumption of intra-tumor glutathione and mitochondrial damage. For the evaluation of OXD and POD-mimicking activities, CMO with ultra low concentration (1 μg ml−1) can rapidly catalyze the color reaction of 3,3′,5,5′-tetramethylbenzidine (TMB) hydrochloride and reach the reaction termination in a very short time (1 s). Moreover, the release and overload of Ca2+ strengthen the tumor cell death. Exogenous ultrasound stimulation further amplifies the enzyodynamic-Ca2+ overload synergistic tumor-therapeutic efficacy. In vitro and in vivo results affirm the transcendent antineoplastic outcomes of CMO. Meanwhile, the existence of Mn2+ endows nanoenzyme with T1-weighted MR imaging capacity. This work provides new strategies for efficient enzyme-mimicking activity and tumor synergistic treatment based on new perspectives on the engineering of multifunctional therapeutic nanomedicine.

Saikosaponin-d Mediates FOXG1 to Reverse Docetaxel Resistance in Prostate Cancer through Oxidative Phosphorylation

BackgroundProstate cancer (PCa), a prevalent malignancy worldwide, is frequently identified in advanced stages due to the absence of distinctive early symptoms, thereby culminating in the development of chemotherapy-induced drug resistance. Exploring novel resistance mechanisms and identifying new therapeutic agents can facilitate the advancement of more efficacious strategies for PCa treatment. MethodsBioinformatics analysis was employed to investigate the expression of FOXG1 in PCa tissues. Subsequently, qRT-PCR was utilized to validate FOXG1 mRNA expression levels in corresponding PCa cell lines. FOXG1 knockdown was performed, and cell proliferation was assessed using CCK-8 assays, while cell migration and invasion capabilities were evaluated through wound healing and Transwell assays. Western blot and Seahorse analyzer were used to measure oxidative phosphorylation (OXPHOS) levels. Additionally, to explore potential approaches to alleviate PCa drug resistance, this study assessed the impact of biologically active saikosaponin-d (SSd) on PCa malignant progression and resistance by regulating FOXG1 expression. ResultsFOXG1 exhibited high expression in PCa tissues and cell lines. Knockdown of FOXG1 inhibited the proliferation, migration, and invasion of PCa cells, while FOXG1 overexpression had the opposite effect and promoted OXPHOS levels. The addition of an OXPHOS inhibitor prevented this outcome. Finally, SSd was shown to suppress FOXG1 expression and reverse docetaxel resistance in PCa cells through the OXPHOS pathway. ConclusionThis work demonstrated that SSd mediated FOXG1 to reverse malignant progression and docetaxel resistance in PCa through OXPHOS.

Inorganic sulfides prevent osimertinib-induced mitochondrial dysfunction in human iPS cell-derived cardiomyocytes

Despite the widespread recognition of the global concern regarding the onset of cardiovascular diseases in a significant number of patients following cancer treatment, definitive strategies for prevention and treatment remain elusive. In this study, we established systems to evaluate the influence of anti-cancer drugs on the quality control of mitochondria, pivotal for energy metabolism, using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor used for treatment in lung cancer, reportedly increases the risk of cardiovascular disease. However, its underlying mechanism is largely unknown. Here, we found that the treatment of hiPSC-CMs with osimertinib and doxorubicin, but not trastuzumab and cisplatin, revealed a concentration-dependent impairment of respiratory function accompanied by mitochondrial fission. We previously reported the significant role of sulfur metabolism in maintaining mitochondrial quality in the heart. Co-treatment with various inorganic sulfur donors (Na2S, Na2S2, Na2S3) alongside anti-cancer drugs demonstrated that Na2S attenuated the cardiotoxicity of osimertinib but not doxorubicin. Osimertinib decreased intracellular reduced sulfur levels, while Na2S treatment suppressed the sulfur leakage, suggesting its potential in mitigating osimertinib-induced cardiotoxicity. These results imply the prospect of inorganic sulfides, such as Na2S, as a seed for precision pharmacotherapy to alleviate osimertinib's cardiotoxic effects.

A Novel Strategy for Glioblastoma Treatment by Natural Bioactive Molecules Showed a Highly Effective Anti-Cancer Potential

A Novel Strategy for Glioblastoma Treatment by Natural Bioactive Molecules Showed a Highly Effective Anti-Cancer Potential

Unlocking the potential of bispecific ADCs for targeted cancer therapy.

Antibody-drug conjugates (ADCs) are biologically targeted drugs composed of antibodies and cytotoxic drugs connected by linkers. These innovative compounds enable precise drug delivery to tumor cells, minimizing harm to normal tissues and offering excellent prospects for cancer treatment. However, monoclonal antibody-based ADCs still present challenges, especially in terms of balancing efficacy and safety. Bispecific antibodies are alternatives to monoclonal antibodies and exhibit superior internalization and selectivity, producing ADCs with increased safety and therapeutic efficacy. In this review, we present available evidence and future prospects regarding the use of bispecific ADCs for cancer treatment, including a comprehensive overview of bispecific ADCs that are currently in clinical trials. We offer insights into the future development of bispecific ADCs to provide novel strategies for cancer treatment.

Phthalocyanine-enabled technologies for water treatment and disinfection strategies

Water treatment and disinfection are critical factors in ensuring a safe and sustainable water supply. Phthalocyanines (Pcs), a class of versatile and robust organic compounds, have garnered significant attention for their application in various water treatment processes. This review paper offers a groundbreaking investigation of Pc-enabled technologies within the domain of water treatment applications. The core aim of this review is to meticulously analyze the chemical and optical properties of Pcs, elucidate their photosensitization mechanism and establish the crucial connection between their chemical structure and photodynamic efficacy. The various modes of Pcs application in water treatment processes - whether in solution, immobilized, or integrated into water treatment membranes - emphasizing the strategies for their integration and effectiveness in disinfection and decontamination has also been extensively investigated. Moreover, it sheds light on the latest advancements and challenges in the field, providing valuable insights into future research for employing Pcs in environmentally sustainable water treatment methods.

Poly-β-hydroxybutyrate supplementation enhanced the growth and immune responses of juvenile Nile tilapia (Oreochromis niloticus)

Development of alternative disease treatment and prevention strategies has received considerable attention in recent years due to frequent epizootic outbreaks in modern intensive aquaculture. Poly-β-hydroxybutyrate (PHB) is a biopolymer synthesized by some bacteria with potential immunostimulatory effects. This study analyzed the potential of PHB as an immunomodulator in juvenile Nile tilapia utilizing in vitro and in vivo approaches. Head-kidney-derived macrophage production of intra- and extra-cellular superoxide anion exhibited significant linear and quadratic relationships with graded doses (0.0, 0.5, 1.0, 2.0, 4.0 and 8.0 mM) of a PHB precursor, 3-hydroxybutryate (3HB). Additionally, lyophilized PHB-synthesizing bacteria, Zobellella denitrificans (ZD1), were supplemented to a practical basal diet for Nile tilapia (36% crude protein and 6% crude lipid) to produce five isonitrogenous and isolipidic experimental diets containing PHB in five stepwise increments (0.125, 0.25, 0.5, 1.0, and 2.0% of dry-diet weight). After termination of the feeding trial, Nile tilapia exhibited dose-dependent linear and quadratic relationships in percentage weight gain, as well as feed efficiency, protein conversion efficiency, and hepatosomatic index. Finally, PHB-supplemented diets did significantly modulate intestinal microbiota composition. In conclusion, Nile tilapia exhibited enhanced growth parameters, condition factors, immunological responses, and intestinal microbiota modulation when fed PHB, with the optimal inclusion level determined to be 1% of dry diet.