No abstract available.
Bone Marrow* ; Sarcoma, Ewing*

No abstract available.
Cytogenetics* ; Humans ; Leukemia*

No abstract available.
beta-Thalassemia*

The present study was carried out to examine the mechanisms of the synergistic interaction of PAF and A23187 mediated platelet aggregation. We found that platelet aggregation mediated by subthreshold concentrations of PAF (5 nM) and A23187 (1 micrometer) was inhibited by PAF receptor blocker (WEB 2086, IC50=0.65 micrometer) and calcium channel blockers, diltiazem (IC50=13 micrometer) and verapamil (IC50=18 micrometer). Pretreatment of platelets with PAF and A23187 induced rise in intracellular calcium and this effect was also blocked by verapamil. While examining the role of the down stream signaling pathways, we found that platelet aggregation induced by the co-addition of PAF and A23187 was also inhibited by low concentrations of phospholipase C (PLC) inhibitor (U73122; IC50 = 10 micrometer), a cyclooxygenase inhibitor (indomethacin; IC50=0.2 micrometer) and inhibitor of TLCK, herbimycin A with IC50 value of 5 micrometer. The effect was also inhibited by a specific TXA2 receptor antagonist, SQ 29548 with very low IC50 value of 0.05 micrometer. However, the inhibitors of MAP kinase, PD98059 and protein kinase C, chelerythrine had no effect on PAF and A23187-induced platelet aggregation. These data suggest that the synergism between PAF and A23187 in platelet aggregation involves activation of thromboxane and tyrosine kinase pathways.
Blood Platelets/*drug effects ; Calcimycin/*pharmacology ; Humans ; Indomethacin/pharmacology ; Ionophores/pharmacology ; Platelet Activating Factor/metabolism/*pharmacology ; Platelet Aggregation/*physiology ; Protein-Tyrosine Kinase/antagonists & inhibitors/*physiology ; Quinones/pharmacology ; Research Support, Non-U.S. Gov't ; Thromboxane A2/*physiology ; Verapamil/pharmacology

Type 2 diabetes mellitus (T2DM) management demands innovative strategies that address its complex nature. Telerehabilitation and conventional rehabilitation, which utilize wearable devices, represent promising avenues in this regard. This narrative review synthesizes the current literature to comprehensively compare these modalities in terms of accessibility, monitoring mechanisms, patient adherence, cost-effectiveness, and social support. Telerehabilitation offers unparalleled convenience, real-time monitoring, and personalized feedback through wearables, thereby fostering greater patient engagement and adherence compared to conventional rehabilitation. However, conventional rehabilitation provides face-to-face interactions, immediate feedback, and a more personalized touch, albeit with logistical challenges and higher costs. This review emphasizes the significance of patient preferences, technological access, and healthcare infrastructure in selecting the appropriate approach. It also calls for further research into long-term outcomes, cost-effectiveness, and the optimal integration of wearable technology in diabetes management programs. Ultimately, both telerehabilitation and conventional rehabilitation demonstrate considerable potential in empowering individuals with T2DM, underlining the imperative for tailored and patient-centric interventions in diabetes care. The review also stresses the significance of integrating patient preferences and their level of comfort with technology when deciding on treatment approaches. It also takes into account the diverse socioeconomic contexts and healthcare infrastructures globally, which can affect the viability and efficacy of both telerehabilitation and conventional rehabilitation. Moreover, the integration of wearable technology in diabetes management programs holds promise for enhancing self-management capabilities and promoting healthier lifestyles. However, it is essential to tackle prospective discrepancies in access to these technologies and ensure fair distribution. Looking forward, ongoing research efforts should focus on justifying long-term outcomes, optimizing cost-effectiveness, and refining implementation strategies to maximize the benefits of both modalities.

Type 2 diabetes mellitus (T2DM) management demands innovative strategies that address its complex nature. Telerehabilitation and conventional rehabilitation, which utilize wearable devices, represent promising avenues in this regard. This narrative review synthesizes the current literature to comprehensively compare these modalities in terms of accessibility, monitoring mechanisms, patient adherence, cost-effectiveness, and social support. Telerehabilitation offers unparalleled convenience, real-time monitoring, and personalized feedback through wearables, thereby fostering greater patient engagement and adherence compared to conventional rehabilitation. However, conventional rehabilitation provides face-to-face interactions, immediate feedback, and a more personalized touch, albeit with logistical challenges and higher costs. This review emphasizes the significance of patient preferences, technological access, and healthcare infrastructure in selecting the appropriate approach. It also calls for further research into long-term outcomes, cost-effectiveness, and the optimal integration of wearable technology in diabetes management programs. Ultimately, both telerehabilitation and conventional rehabilitation demonstrate considerable potential in empowering individuals with T2DM, underlining the imperative for tailored and patient-centric interventions in diabetes care. The review also stresses the significance of integrating patient preferences and their level of comfort with technology when deciding on treatment approaches. It also takes into account the diverse socioeconomic contexts and healthcare infrastructures globally, which can affect the viability and efficacy of both telerehabilitation and conventional rehabilitation. Moreover, the integration of wearable technology in diabetes management programs holds promise for enhancing self-management capabilities and promoting healthier lifestyles. However, it is essential to tackle prospective discrepancies in access to these technologies and ensure fair distribution. Looking forward, ongoing research efforts should focus on justifying long-term outcomes, optimizing cost-effectiveness, and refining implementation strategies to maximize the benefits of both modalities.

Type 2 diabetes mellitus (T2DM) management demands innovative strategies that address its complex nature. Telerehabilitation and conventional rehabilitation, which utilize wearable devices, represent promising avenues in this regard. This narrative review synthesizes the current literature to comprehensively compare these modalities in terms of accessibility, monitoring mechanisms, patient adherence, cost-effectiveness, and social support. Telerehabilitation offers unparalleled convenience, real-time monitoring, and personalized feedback through wearables, thereby fostering greater patient engagement and adherence compared to conventional rehabilitation. However, conventional rehabilitation provides face-to-face interactions, immediate feedback, and a more personalized touch, albeit with logistical challenges and higher costs. This review emphasizes the significance of patient preferences, technological access, and healthcare infrastructure in selecting the appropriate approach. It also calls for further research into long-term outcomes, cost-effectiveness, and the optimal integration of wearable technology in diabetes management programs. Ultimately, both telerehabilitation and conventional rehabilitation demonstrate considerable potential in empowering individuals with T2DM, underlining the imperative for tailored and patient-centric interventions in diabetes care. The review also stresses the significance of integrating patient preferences and their level of comfort with technology when deciding on treatment approaches. It also takes into account the diverse socioeconomic contexts and healthcare infrastructures globally, which can affect the viability and efficacy of both telerehabilitation and conventional rehabilitation. Moreover, the integration of wearable technology in diabetes management programs holds promise for enhancing self-management capabilities and promoting healthier lifestyles. However, it is essential to tackle prospective discrepancies in access to these technologies and ensure fair distribution. Looking forward, ongoing research efforts should focus on justifying long-term outcomes, optimizing cost-effectiveness, and refining implementation strategies to maximize the benefits of both modalities.

Our recent studies have shown that co-activation of Gq and Gi proteins by 5-hydroxytryptamine (5-HT) and adrenaline show synergism in human platelet aggregation. This study was conducted to examine the mechanism(s) of synergistic interaction of 5-HT and platelet activating factor (PAF) in human platelets. We show that PAF, but not 5-HT, increased platelet aggregation in a concentration-dependent manner. However, low concentrations of 5-HT (2 microM) potentiated platelet aggregation induced by subthreshold concentration of PAF (40 nM) indicating a synergistic interaction between the two agonists and this synergism was blocked by receptor antagonists to either 5-HT or PAF. 5-HT also potentiated the effect of PAF on thromboxane A2 (TXA2) formation and phosphorylation of extracellularly regulated mitogen-activated protein kinases (ERK1/2). The synergism of 5-HT and PAF in platelet aggregation was inhibited by calcium (Ca2+) channel blockers, verapamil and diltiazem, phospholipase C (PLC) inhibitor, U73122, cyclooxygenase (COX) inhibitor, indomethacin, and MEK inhibitor, PD98059. These data suggest that synergistic effect of 5-HT and PAF on human platelet aggregation involves activation of PLC/Ca2+, COX and MAP kinase pathways.
Diltiazem/pharmacology ; Dose-Response Relationship, Drug ; Drug Synergism ; Estrenes/pharmacology ; Flavones/pharmacology ; Human ; In Vitro ; Indomethacin/pharmacology ; Kinetics ; Mitogen-Activated Protein Kinases/metabolism ; Phosphorylation/drug effects ; Platelet Activating Factor/*pharmacology ; Platelet Activation/drug effects ; Platelet Aggregation/*drug effects/physiology ; Pyrrolidinones/pharmacology ; Serotonin/*pharmacology ; Thromboxane A2/biosynthesis ; Verapamil/pharmacology

Our recent studies have shown that co-activation of Gq and Gi proteins by 5-hydroxytryptamine (5-HT) and adrenaline show synergism in human platelet aggregation. This study was conducted to examine the mechanism(s) of synergistic interaction of 5-HT and platelet activating factor (PAF) in human platelets. We show that PAF, but not 5-HT, increased platelet aggregation in a concentration-dependent manner. However, low concentrations of 5-HT (2 microM) potentiated platelet aggregation induced by subthreshold concentration of PAF (40 nM) indicating a synergistic interaction between the two agonists and this synergism was blocked by receptor antagonists to either 5-HT or PAF. 5-HT also potentiated the effect of PAF on thromboxane A2 (TXA2) formation and phosphorylation of extracellularly regulated mitogen-activated protein kinases (ERK1/2). The synergism of 5-HT and PAF in platelet aggregation was inhibited by calcium (Ca2+) channel blockers, verapamil and diltiazem, phospholipase C (PLC) inhibitor, U73122, cyclooxygenase (COX) inhibitor, indomethacin, and MEK inhibitor, PD98059. These data suggest that synergistic effect of 5-HT and PAF on human platelet aggregation involves activation of PLC/Ca2+, COX and MAP kinase pathways.
Diltiazem/pharmacology ; Dose-Response Relationship, Drug ; Drug Synergism ; Estrenes/pharmacology ; Flavones/pharmacology ; Human ; In Vitro ; Indomethacin/pharmacology ; Kinetics ; Mitogen-Activated Protein Kinases/metabolism ; Phosphorylation/drug effects ; Platelet Activating Factor/*pharmacology ; Platelet Activation/drug effects ; Platelet Aggregation/*drug effects/physiology ; Pyrrolidinones/pharmacology ; Serotonin/*pharmacology ; Thromboxane A2/biosynthesis ; Verapamil/pharmacology

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant global health issue, affecting over 30% of the population worldwide due to the rising prevalence of metabolic risk factors such as obesity and type 2 diabetes mellitus. This spectrum of liver disease ranges from isolated steatosis to more severe forms such as steatohepatitis, fibrosis, and cirrhosis. Recent studies highlight the role of gut microbiota in MASLD pathogenesis, showing that dysbiosis significantly impacts metabolic health and the progression of liver disease. This review critically evaluates current microbiome-centered therapies in MASLD management, including prebiotics, probiotics, synbiotics, fecal microbiota transplantation, and emerging therapies such as engineered bacteria and bacteriophage therapy. We explore the scientific rationale, clinical evidence, and potential mechanisms by which these interventions influence MASLD. The gut-liver axis is crucial in MASLD, with notable changes in microbiome composition linked to disease progression. For instance, specific microbial profiles and reduced alpha diversity are associated with MASLD severity. Therapeutic strategies targeting the microbiome could modulate disease progression by improving gut permeability, reducing endotoxin-producing bacteria, and altering bile acid metabolism. Although promising, these therapies require further research to fully understand their mechanisms and optimize their efficacy. This review integrates findings from clinical trials and experimental studies, providing a comprehensive overview of microbiome-centered therapies’ potential in managing MASLD. Future research should focus on personalized strategies, utilizing microbiome features, blood metabolites, and customized dietary interventions to enhance the effectiveness of these therapies.