Therapeutic Modalities Research Articles

Disrupting glioblastoma networks with tumor treating fields (TTFields) in in vitro models.

This study investigates the biological effect of Tumor Treating Fields (TTFields) on key drivers of glioblastoma's malignancy-tumor microtube (TM) formation-and on the function and overall integrity of the tumor cell network. Using a two-dimensional monoculture GB cell network model (2DTM) of primary glioblastoma cell (GBC) cultures (S24, BG5 or T269), we evaluated the effects of TTFields on cell density, interconnectivity and structural integrity of the tumor network. We also analyzed calcium (Ca2+) transient dynamics and network morphology, validating findings in patient-derived tumoroids and brain tumor organoids. In the 2DTM assay, TTFields reduced cell density by 85-88% and disrupted network interconnectivity, particularly in cells with multiple TMs. A "crooked TM" phenotype emerged in 5-6% of treated cells, rarely seen in controls. Ca2+ transients were significantly compromised, with global Ca2+ activity reduced by 51-83%, active and periodic cells by over 50%, and intercellular co-activity by 52% in S24, and almost completely in BG5 GBCs. The effects were more pronounced at 200kHz compared to a 50kHz TTFields. Similar reductions in Ca2+ activity were observed in patient-derived tumoroids. In brain tumor organoids, TTFields significantly reduced tumor cell proliferation and infiltration. Our comprehensive study provides new insights into the multiple effects of Inovitro-modeled TTFields on glioma progression, morphology and network dynamics in vitro. Future in vivo studies to verify our in vitro findings may provide the basis for a deeper understanding and optimization of TTFields as a therapeutic modality in the treatment of GB.

Current findings on the antitumor effects of metformin on esophageal squamous cell carcinoma (Review).

Esophageal squamous cell carcinoma (ESCC) is an intractable type of cancer that requires novel therapeutic modalities, since the therapeutic outcomes are often inadequate, even in response to multidisciplinary treatment. The antitumor effect of metformin, an antidiabetic drug, has been reported in esophageal cancer; however, its effects are diverse. Since various multidisciplinary therapies are used in ESCC, the antitumor effect of metformin is expected to be synergistic in some treatment strategies. The present review summarizes the antitumor effects of metformin and discusses its use in combination with existing therapies. The present study reviewed relevant studies where the molecular targets of metformin (AMPK and inflammatory system signals) were described, followed by the classification and organization of its antitumor effects, and subsequently summarized the current research on its antitumor effects, especially in ESCC. A number of studies have reported that metformin prevents the development of ESCC and exerts its antitumor effects through various pathways. In addition, metformin has been shown to inhibit tumor growth, induce apoptosis, inhibit cancer cell invasion, migration and angiogenesis into the tumor, and decrease tumor malignancy, such as metastasis. Furthermore, it may modulate host tumor immunity in a tumor-suppressive manner and is expected to improve prognosis following treatment for ESCC. Notably, metformin may be beneficial in combination with chemotherapy, such as cisplatin, and radiation. By contrast, it has been shown to potentially induce resistance to 5-fluorouracil. Finally, the effects of metformin in combination with other therapies are discussed in the present study, and perspectives on the potential benefits of metformin for future ESCC treatment are presented. In conclusion, the present review may be useful in improving the understanding of the wide range of antitumor effects of metformin. Although some concerning points remain, using metformin in ESCC treatment could be promising. Notably, more knowledge needs to be accumulated regarding the effects of metformin on ESCC.

Safety and efficacy of CT-guided percutaneous radiofrequency ablation for non-small cell lung cancer: a single-center, single-arm analysis.

Non-small cell lung cancer (NSCLC) is a prevalent malignant tumor, and the commonly treatment modalities include surgery, radiotherapy, chemotherapy, etc. Currently, CT-guided percutaneous radiofrequency ablation (RFA) for the treatment of cancers has been widely performed. This study aimed to evaluate the safety and efficacy of this therapy in NSCLC patients. Thirty-five NSCLC patients were enrolled in this study and all received CT-guided percutaneous RFA therapy. The outcome measures included the changes in forced respiratory volume in the first second (FEV1), total lung volume (TLC), lesion size and computed tomography (CT) values of the region of interest (ROI) before and after treatment. The main efficacy measures comprised complete tumor ablation and local recurrence after initial treatment, as well as the objective response rate (ORR) and disease control rate (DCR) after 6 months of treatment. After receiving CT-guided percutaneous RFA therapy, the target lesion was effectively controlled and CT values gradually decreased. Besides, no significant changes were observed in the patient's lung function, postoperative complications were experienced by a total of 10 patients, primarily including pneumothorax, infection, lung hollowing. Fortunately, all these complications were successfully managed with appropriate treatment. Following the initial RFA treatment, 31 patients (88.57%) achieved complete ablation, while 6 patients experienced local recurrence. After 6 months of treatment, the ORR and DCR were found to be 68.57% and 82.86% respectively. CT-guided percutaneous RFA has demonstrated favorable safety and efficacy in the treatment of patients with NSCLC at different stages, which represented a promising therapeutic modality.

Advances in immunotherapy for mucosal melanoma: harnessing immune checkpoint inhibitors for improved treatment outcomes

Mucosal melanoma (MM) poses a significant clinical challenge due to its aggressive nature and limited treatment options. In recent years, immunotherapy has emerged as a promising strategy for MM, with a particular focus on immune checkpoint inhibitors such as PD-1 and CTLA-4 inhibitors. These inhibitors have demonstrated substantial efficacy by harnessing the body’s immune response against tumors. Moreover, adoptive cell transfer (ACT), anti-angiogenic therapy, and combination therapies have garnered attention for their potential in MM treatment. ACT involves modifying T cells to target melanoma cells, showing promising antitumor activity. Anti-angiogenic therapy aims to impede tumor growth by inhibiting angiogenesis, while combination therapies, including immune checkpoint inhibitors and targeted therapies, offer a multifaceted approach to overcome treatment resistance. This comprehensive review explores the advancements in immunotherapy for MM, highlighting the role of diverse therapeutic modalities in enhancing treatment outcomes and addressing the challenges posed by this aggressive malignancy.

Exosomes Exposed: Overview Systematic Review on Evidence Versus Expectation in Aesthetic and Regenerative Medicine.

Exosomes, diminutive extracellular vesicles, are integral to intercellular communication, harbouring potential for applications in regenerative medicine and aesthetic interventions. The field, however, grapples with the complexities of harmonising exosome characterisation protocols and safeguarding therapeutic integrity. In this scholarly overview, systematic adherence to the Cochrane Collaboration and Preferred Reporting Items for Overviews of Reviews guidelines was observed, scrutinising the congruence of exosome-related therapies with the Minimal Information for Studies of Extracellular Vesicles standards delineated by the International Society for Extracellular Vesicles, alongside criteria set forth by the International Society for Cell Therapy and the International Society for Stem Cell Research. A meticulous search strategy spanning databases such as PubMed, Scopus, Web of Science, EMBASE, and Cochrane database was employed to encapsulate studies pertinent to the isolation, characterisation, and functional assessment of exosomes. The initial search yielded 225 articles, of which 17 systematic reviews were selected based on predefined criteria, encompassing 556 primary studies. Notwithstanding the acknowledged therapeutic promise of exosome modalities, the synthesis illuminated a prevalent deficiency in adherence to established reporting and experimental benchmarks, notably in exosome source characterisation and bioactive constituent delineation. A critical appraisal employing the AMSTAR-2 tool underscored a pervasive shortfall in methodological rigour. This review accentuates the imperative for stringent methodological standardisation within exosome research to fortify the validity and reproducibility of empirical findings. Amidst the burgeoning therapeutic optimism, the discipline must rectify methodological disparities and comply with regulatory mandates, ensuring the ethically sound and scientifically robust advancement of exosome-based therapeutic modalities. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Combinatorial approach of cannabidiol and active-targeted-mediated photodynamic therapy in malignant melanoma treatment.

Malignant melanoma (MM) continues to claim millions of lives around the world due to its limited therapeutic alternatives. Photodynamic therapy (PDT) has gained popularity in cancer treatment due it increased potency and low off-target toxicity. Studies have pointed out that the heterogeneity of MM tumours reduces the efficacy of current therapeutic approaches, including PDT, leading to high chances of recurrences post-treatment. Accumulating evidence suggests that cannabidiol (CBD), a non-psychoactive derivative of cannabis, can synergise with various anticancer agents to increase their efficacy. However, CBD demonstrates low bioavailability, which is attributed to factors relating to poor water compatibility, poor absorption and rapid metabolism. Nanotechnology offers tools that address these issues and enhance the biological efficiency and targeted specificity of anticancer agents. Herein, we highlighted the standard therapeutic modalities of MM and their pitfalls, as well as pointed out the need for further investigation into PDT combination therapy with CBD.

Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease

BACKGROUND Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality, but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis. Peroxisome proliferator activated receptor (PPAR) α and δ play a key role in lipid metabolism and intestinal barrier homeostasis, which are major contributors to the pathological progression of ALD. Meanwhile, elafibranor (EFN), which is a dual PPARα and PPARδ agonist, has reached a phase III clinical trial for the treatment of metabolic dysfunction-associated steatotic liver disease and primary biliary cholangitis. However, the benefits of EFN for ALD treatment is unknown. AIM To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model. METHODS ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol (EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly (1 mL/kg) for 8 weeks. EFN (3 and 10 mg/kg/day) was orally administered during the experimental period. Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis, fibrosis, and intestinal barrier integrity. The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays. RESULTS The hepatic steatosis, apoptosis, and fibrosis in the ALD mice model were significantly attenuated by EFN treatment. EFN promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells, primarily through PPARα activation. Moreover, EFN inhibited the Kupffer cell-mediated inflammatory response, with blunted hepatic exposure to lipopolysaccharide (LPS) and toll like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling. EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses. The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation. CONCLUSION EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis, enhancing hepatocyte autophagic and antioxidant capacities, and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.

Empagliflozin impact on experimentally induced acetaminophen toxicity: Imprint of mitochondrial dynamics, biogenesis, and cGAS/STING signal in amending liver insult.

Acetaminophen (APAP) is one of the most clinically relevant medications associated with acute liver damage. A prolific deal of research validated the hepatoprotective effect of empagliflozin (EMPA); however, its effect on APAP-induced hepatotoxicity has still not been investigated. In this study, the prospective hepatoprotective impact of EMPA against APAP-induced hepatotoxicity was investigated. Twenty-eight Balb-C mice were assigned to four groups: control, APAP, EMPA10/APAP, and EMPA25/APAP. At the end of the experiment, serum hepatotoxicity biomarkers, MDA level, and GSH content were estimated. Hepatic mitofusin-2 (MFN2), optic atrophy 1 (OPA1), dynamin-related protein 1 (Drp1), and mitochondrial fission 1 protein (FIS1) were immunoassayed. PGC-1α, cGAS, and STING mRNA expression were assessed by real-time PCR. Histopathological changes and immunohistochemistry of INF-β, p-NF-κB, and iNOS were evaluated. APAP treatment caused significant hepatic functional impairment and increased hepatic MDA levels, as well as a concomitant decrease in GSH content. Marked elevation in Drp1 and FIS1 levels, INF-ß, p-NF-κB, and iNOS immunoreactivity, and reduction in MFN2 and OPA1 levels in the APAP-injected group, PGC-1α downregulation, and high expression of cGAS and STING were also documented. EMPA effectively ameliorated APAP-generated structural and functional changes in the liver, restored redox homeostasis and mitochondrial dynamics balance, and enhanced mitochondrial biogenesis, remarkably diminished hepatic expression of cGAS and STING, and elicited a reduction in hepatic inflammation. Moreover, the computational modeling data support the interaction of APAP with antioxidant system-related proteins as well as the interactions of EMPA against Drp1, cGAS, IKKA, and iNOS proteins. Our findings demonstrated for the first time that EMPA has an ameliorative impact against APAP-induced hepatotoxicity in mice via modulation of mitochondrial dynamics, biogenesis, and cGAS/STING-dependent inflammation. Thus, this study concluded that EMPA could be a promising therapeutic modality for acute liver toxicity.

Do antro-duodenal manometry parameters predict clinical response after gastric peroral endoscopic pyloromyotomy in refractory gastroparesis?

Gastric peroral endoscopic pyloromyotomy (G-POEM) is a promising therapeutic modality for refractory gastroparesis (GP). However, as characteristics of suitable patients for G-POEM remain unclear, antro-duodenal manometry (ADM) has been suggested to provide objective parameters for patient selection. The aim of the present study was to identify ADM parameters as predictors for treatment response after G-POEM in refractory GP. Refractory GP patients who underwent a G-POEM between 2017 and 2022 were included. The following ADM parameters were mainly scored: antral hypomotility, pylorospasm, and the presence of neuropathic enteric patterns. Treatment response was defined as a GCSI-score decrease of ≥1 point 12 months after G-POEM. Explorative analyses were performed on potential predictors of response using logistic regression analysis. Sixty patients (52 women, mean age 52 ± 14 years.) with refractory GP (33 idiopathic, 16 diabetic, 11 postsurgical) were included. Clinical response data were available for 52 patients. In 8 out of 60 patients, it was not feasible to advance the catheter beyond the pylorus. Abnormal ADM was found in 46/60 patients (77%). Antral hypomotility and pylorospasm were found in respectively 33% and 12% of patients. At least one neuropathic enteric dysmotility pattern was found in 58% of patients. No differences were found when comparing baseline ADM parameters between clinical response groups at 12 months follow-up. Following explorative analyses, no ADM parameters were identified to predict clinical response 12 months after G-POEM. No ADM parameters were identified as predictors of clinical response after G-POEM in refractory GP patients. Additionally, a high percentage of abnormal ADM tracings was found, in particular with relation to enteric dysmotility, while only a low percentage of patients showed antral hypomotility or pylorospasm.

Radiomics as a tool for prognostic prediction in transarterial chemoembolization for hepatocellular carcinoma: a systematic review and meta-analysis.

Transarterial chemoembolization (TACE) is one of the predominant locoregional therapeutic modalities for addressing hepatocellular carcinoma (HCC). However, achieving precise prognostic predictions and effective patient selection remains a challenging pursuit. The primary objective of this systematic review and meta-analysis is to evaluate the efficacy of radiomics in forecasting the prognosis associated with TACE treatment. A comprehensive exploration of pertinent original studies was undertaken, encompassing databases of PubMed, Web of Scienceand Embase. The studies' quality was meticulously evaluated employing the quality assessment of diagnostic accuracy studies 2 (QUADAS-2), the radiomics quality score (RQS) and the METhodological RadiomICs Score (METRICS). Pooled statistics, along with 95% confidence intervals (95% CI), were computed for sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR). Additionally, a summary receiver operating characteristic curve (sROC) was generated. To discern potential sources of heterogeneity, meta-regression and subgroup analyses were performed. The systematic review incorporated 29 studies, comprising a total of 5483 patients, with 14 studies involving 2691 patients qualifying for inclusion in the meta-analysis. The assessed studies exhibited commendable quality with regard to bias risk, with mean RQS of 12.90 ± 5.13 (35.82% ± 14.25%) and mean METRICS of 62.98% ± 14.58%. The pooled sensitivity was 0.83 (95% CI: 0.78-0.87), specificity was 0.86 (95% CI: 0.79-0.92), PLR was 6.13 (95% CI: 3.79-9.90), and NLR was 0.20 (95% CI: 0.15-0.27). The area under the sROC was 0.90 (95% CI: 0.87-0.93). Significant heterogeneity within all the included studies was observed, while meta-regression and subgroup analyses revealed homogeneous and promising findings in subgroups where principal methodological variables such as modeling algorithms, imaging modalities, and imaging phases were specified. Radiomics models have exhibited robust predictive capabilities concerning prognosis subsequent to TACE, thereby presenting promising prospects for clinical translation.

Gut microbiota regulates gut homeostasis, mucosal immunity and influences immune-related diseases.

The intestinal microbiome constitutes a sophisticated and massive ecosystem pivotal for maintaining gastrointestinal equilibrium and mucosal immunity via diverse pathways. The gut microbiota is continuously reshaped by multiple environmental factors, thereby influencing overall wellbeing or predisposing individuals to disease state. Many observations reveal an altered microbiome composition in individuals with autoimmune conditions, coupled with shifts in metabolic profiles, which has spurred ongoing development of therapeutic interventions targeting the microbiome. This review delineates the microbial consortia of the intestine, their role in sustaining gastrointestinal stability, the association between the microbiome and immune-mediated pathologies, and therapeutic modalities focused on microbiome modulation. We emphasize the entire role of the intestinal microbiome in human health and recommend microbiome modulation as a viable strategy for disease prophylaxis and management. However, the application of gut microbiota modification for the treatment of immune-related diseases, such as fecal microbiota transplantation and probiotics, remain quite challenging. Therefore, more research is needed into the role and mechanisms of these therapeutics.

Integrated multi-omics with machine learning to uncover the intricacies of kidney disease.

The development of omics technologies has driven a profound expansion in the scale of biological data and the increased complexity in internal dimensions, prompting the utilization of machine learning (ML) as a powerful toolkit for extracting knowledge and understanding underlying biological patterns. Kidney disease represents one of the major growing global health threats with intricate pathogenic mechanisms and a lack of precise molecular pathology-based therapeutic modalities. Accordingly, there is a need for advanced high-throughput approaches to capture implicit molecular features and complement current experiments and statistics. This review aims to delineate strategies for integrating multi-omics data with appropriate ML methods, highlighting key clinical translational scenarios, including predicting disease progression risks to improve medical decision-making, comprehensively understanding disease molecular mechanisms, and practical applications of image recognition in renal digital pathology. Examining the benefits and challenges of current integration efforts is expected to shed light on the complexity of kidney disease and advance clinical practice.

Copper Single-Atom-Based Metal-Organic Framework for Ultrasound-Enhanced Nanocatalytic Therapy.

Chemodynamic therapy (CDT) is an emerging therapeutic modality triggered by endogenous substances in the tumor microenvironment (TME) to generate reactive oxygen species. However, the mild acid pH, low H2O2 concentration, and overexpressed glutathione can suppress the CDT efficiency. Herein, ultrasound (US)-triggered Cu2+-based single-atom nanoenzymes (FA-NH2-UiO-66-Cu, FNUC) are constructed with the performance of target and glutathione depletion. In the TME, the single-atom Cu sites of FNUC consume glutathione and the FNUC:Cu+ generates •OH via peroxidase-like activity. The US-activated FNUC exhibits a fast •OH generation rate, a low Michaelis constant, and a large •OH concentration, indicating the cavitation effect of US promotes the •OH generation. Meanwhile, the tumor target of FNUC is confirmed by NIR-II fluorescence imaging, in which it is modified with IR-1061. Combined with the antitumor performance of FNUC in vitro and in vivo, the novel Cu-based SAzymes can achieve efficient and precise cancer treatment.

Imaging light fluence in blood vessels by combining photoacoustic fluctuation imaging and ultrasound power doppler.

Numerous optical biomedical imaging or therapeutic modalities suffer from unknown light fluence distribution at depths. Photoacoustic (PA) imaging enables imaging of blood vessels. At the scale of the acoustic resolution, PA imaging probes the product between the fluence and effective optical absorption that depends on the size or density of blood vessels. In the case of unresolved vessels, fluence and absorption can not be decoupled using PA imaging alone without the use of inverse problems. Thus, we propose combining two modalities that are sensitive to blood vessels to directly image fluence maps within vascularized areas, including in unresolved vessels. To achieve fluence imaging, the combination of photoacoustic fluctuation (PAFI) and Ultrasound Power Doppler (UPD) images is considered. After exposing a new theoretical expression of the UPD image, we establish a fluence imaging method giving quantitative fluence in blood vessels. This method universally applies to arbitrary hematocrit and multi-scale vessel imaging. Using a spherical sparse array, we demonstrate 3D fluence imaging within blood vessels in simulation and experiments which is not possible with PAFI alone. Fluence imaging involves resolution compensation with a PSF filter that is compared to alternative simpler corrections. Overall, we show that combining PAFI and UPD has the potential for real-time light dosimetry or could enhance quantitative inverse problems in photoacoustic imaging.

Neurological Complications of COVID-19: Unraveling the Pathophysiological Underpinnings and Therapeutic Implications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19), induced a global pandemic with a diverse array of clinical manifestations. While the acute phase of the pandemic may be waning, the intricacies of COVID-19′s impact on neurological health remain a crucial area of investigation. Early recognition of the spectrum of COVID-19 symptoms, ranging from mild fever and cough to life-threatening respiratory distress and multi-organ failure, underscored the significance of neurological complications, including anosmia, seizures, stroke, disorientation, encephalopathy, and paralysis. Notably, patients requiring intensive care unit (ICU) admission due to neurological challenges or due to them exhibiting neurological abnormalities in the ICU have shown increased mortality rates. COVID-19 can lead to a range of neurological complications such as anosmia, stroke, paralysis, cranial nerve deficits, encephalopathy, delirium, meningitis, seizures, etc., in affected patients. This review elucidates the burgeoning landscape of neurological sequelae associated with SARS-CoV-2 infection and explores the underlying neurobiological mechanisms driving these diverse manifestations. A meticulous examination of potential neuroinvasion routes by SARS-CoV-2 underscores the intricate interplay between the virus and the nervous system. Moreover, we dissect the diverse neurological manifestations emphasizing the necessity of a multifaceted approach to understanding the disease’s neurological footprint. In addition to elucidating the pathophysiological underpinnings, this review surveys current therapeutic modalities and delineates prospective avenues for neuro-COVID research. By integrating epidemiological, clinical, and diagnostic parameters, we endeavor to foster a comprehensive analysis of the nexus between COVID-19 and neurological health, thereby laying the groundwork for targeted therapeutic interventions and long-term management strategies.

IN SILICO TRIAL APPROACHES BETWEEN PHYTOCHEMICAL COMPOSITION OF VERBENA OFFICINALIS AND LIVER CANCER TARGETS

Objective: The abundance of bioactive metabolites in Verbena officinalis explains the biological benefits and folkloric use of the plant. Liver cancer is an extremely heterogeneous malignant disease compared to other defined tumors. To explore the potential therapeutic value of bioactive metabolites in Verbena officinalis, this study aimed to filter secondary metabolites, conduct ADME-Tox assessments, perform drug similarity tests, and analyze with molecular dynamic simulations. The objective was to evaluate how potential drug candidates derived from Verbena officinalis behave in biological systems and assess their potential toxicity risks. Material and Method: Ligands selected from the ADME assay were utilized in in silico molecular docking studies against Glucose-6-phosphate dehydrogenase enzyme in the oxidative part of the pentose phosphate pathway, which is crucial for liver diseases. These studies were conducted using Autodock Vina embedded in Chimera 1.16. Molecular dynamics simulations were performed with the AMBER16. Result and Discussion: When the ADME test results were evaluated, 88 secondary metabolites were identified as ligands. Among all the ligands evaluated against Glucose-6-phosphate dehydrogenase enzyme, which is the key enzyme of the pentose phosphate pathway, quercetin flavonoid was determined to be the most active ligand with a docking score of -8.1 kcal/mol and binding energy of -118.51 kcal/mol. A molecular dynamics simulation performed for 300 nanoseconds confirmed that quercetin can remain stable in its microenvironment. The activity of this metabolite is worthy of further testing in vitro and in vivo as it may highlight a therapeutic modality within the pentose phosphate pathway.

Decision-making in non-invasive neuromodulation in children

INTRODUCTION: Electrical and magnetic stimulation of the nervous system has been used to treat cerebral palsy, autism spectrum disorder, attention deficit hyperactivity disorder, among other childhood conditions. OBJECTIVES: This infographic was designed to elucidate the decision-making process entailed in selecting neuromodulation protocols for children. METHODS: The development of this infographic was guided by the principles of several healthcare philosophies: (1) the Biopsychosocial Model of the International Classification of Functioning, Disability, and Health;1 (2) Patient- and Family-Centered Practice;2 (3) Evidence-Based Practice;3,4 and (4) the SMART model (Specific, Measurable, Attainable, Realistic/Relevant and Timely outcome) for establishing therapeutic goals.5 RESULTS: This visual tool delineated value points that should be considered before initiating any neuromodulation treatment, conceptualized within a structured framework across various levels, including screening, feasibility and safety assessment, selection of a "SMART" outcome, evaluation of complaints, protocol definition, risks clarification, assessment of benefits and cost-effectiveness, and collaborative and empowered participation of parents/caregivers. CONCLUSION: Neuromodulation protocols’ definitions involve a complex process, encompassing choices related to techniques, targets, parameters, distribution and number of sessions, and the potential incorporation of other therapeutic modalities. This process must be tailored to specific objectives to ensure that treatment can yield optimal results within the users' functional conditions. Our infographic can serve as a tool for comprehensively visualizing the entire process and making well-informed choices in a clear, concise, and organized manner. Nevertheless, it is essential to acknowledge that this model is not flawless and should be refined further to advance toward more humanized and responsible care.

Advancing Tumor-Targeted Chemo-Immunotherapy: Development of the CAR-M-derived Exosome-Drug Conjugate.

Traditional antibody-drug conjugates (ADCs) mainly suppress tumor growth through either chemotherapy with cytotoxic payloads or immunotherapy with immuno-modulators. However, a single therapeutic modality may limit their exploration. Herein, we developed a new type of drug conjugate termed CAR-EDC (CAR-M-derived exosome-drug conjugate) by using CAR-exosomes from CAR-M cells as the targeting drug carrier that contains a high level of CXCL10. CAR-exosomes could significantly enhance the immunological activation and migratory capacity of T lymphocytes and promote their differentiation into CD8+ T cells. It also increased the proportion of M1 macrophages. The CAR-EDC, covalently loaded with SN-38, was internalized into Raji cells through endocytosis mediated by the CAR molecules. It exerted excellent antitumor activity in vivo by virtue of not only chemotherapy by SN38 but also immunotherapy by CXCL10-mediated antitumor immunity. Generally, this study provides an exosome-drug conjugate system with enhanced antitumor effects over traditional ADCs through the synergism of chemotherapy and immunotherapy.

Case Report: Gallstone ileus management - Case report and review of the literature

Gallstone ileus, a rare complication of cholelithiasis, presents significant morbidity and mortality challenges, with no established consensus on optimal management. This study aimed to highlight the complexities surrounding its occurrence and emphasize the need for tailored therapeutic strategies. An 88-year-old female, with a history of type 2 diabetes mellitus presented with diffuse abdominal pain and vomiting. Clinical evaluation revealed signs of small-bowel obstruction. Radiological assessments, including Computed Tomography CT) scans, confirmed biliary ileus, showcasing a sizable gallstone causing subacute obstruction. Emergency surgery involving enterolithotomy was performed, successfully addressing the immediate concerns. Postoperative follow-up demonstrated a one-year asymptomatic period, emphasizing the effectiveness of the chosen intervention. Gallstone ileus typically follows acute cholecystitis, leading to gallstone erosion and fistula formation commonly in the duodenum. Diagnosis is challenging because of nonspecific symptoms, necessitating a high index of suspicion. Computed tomography (CT) plays a pivotal role in accurate and rapid diagnoses. This study delves into the intricate details of gallstone ileus presentation, complications, and the debate surrounding optimal surgical management, acknowledging the effectiveness of the two-stage procedure and emerging laparoscopic approaches. This case provides valuable insights into the intricate facets of gallstone ileus and emphasizes the need for individualized treatment strategies. Successful management, as demonstrated in our case, underscores the importance of considering patient-specific factors when choosing between the surgical approaches. This study supports recent reports advocating for laparoscopic interventions, encouraging further exploration of evolving therapeutic modalities for gallstone ileus.

Effects of Kinesio Taping on Neck Pain: A Meta-Analysis and Systematic Review of Randomized Controlled Trials.

Neck pain constitutes a prevalent and burdensome health issue, substantially impairing patients' quality of life and functional capabilities. Kinesio taping (KT), a commonly employed intervention within physical therapy, holds promise for mitigating such symptoms; however, a comprehensive evaluation of its efficacy and evidence base is lacking. Therefore, this study endeavors to systematically investigate the therapeutic effects of KT on both subjective neck pain intensity and objective measures of physical activity limitations through a rigorous meta-analytic approach. By synthesizing existing literature and scrutinizing methodological nuances, we aim to furnish healthcare practitioners with evidence-informed insights, facilitating more judicious clinical decision-making and optimizing patient outcomes. According to the PRISMA guidelines, we conducted searches on PubMed, Cochrane Library, Embase, and Web of Science for randomized controlled trials (RCTs) investigating the efficacy of KT in treating neck pain. Screening was performed based on predefined inclusion and exclusion criteria. Characteristics of the included RCTs were extracted. Trial heterogeneity was assessed using the I2 statistic. Meta-analysis was conducted using Stata 17 software. Risk of bias and methodological quality were evaluated using the Cochrane Risk of Bias 2 tool and the PEDro scale, respectively. In our analysis of 10 RCTs involving 620 patients meeting our inclusion criteria, KT demonstrated significant beneficial effects on neck pain, notably surpassing conventional treatment (weighted mean difference = -0.897, 95% CI -1.30 to -0.49, P < 0.001). Subgroup analysis further revealed that KT exhibited particularly pronounced efficacy in the treatment of nonspecific neck pain and mechanical neck pain, with a more substantial effect observed after 4 weeks of KT intervention compared to 1 week. Moreover, KT demonstrated superior efficacy in alleviating pain symptoms compared to both conventional treatment and sham interventions. KT has demonstrated efficacy in reducing neck pain and improving cervical dysfunction among patients. Prolonged KT treatment or its combination with other therapeutic modalities may potentially enhance therapeutic outcomes. PROSPERO CRD42024524685.