Pharmacological Treatment Research Articles

Efficacy of Lemborexant in Adults ≥ 65 Years of Age with Insomnia Disorder.

Pharmacologic treatments are available to treat insomnia, a common and burdensome sleep disorder, but may be contraindicated in older adults who are prone to side effects from sleep-promoting drugs. These analyses of sleep diary data from Study E2006-G000-303 (Study 303) investigated the benefits of lemborexant 5mg (LEM5) and 10mg (LEM10) in the subgroup age ≥ 65years with insomnia. Study 303, a 12-month, double-blind study of LEM5 and LEM10 in adults (age ≥ 18years) with insomnia disorder (sleep onset and/or maintenance difficulties) assessed subject-reported (subjective) sleep-onset latency (sSOL), sleep efficiency (sSE), wake after sleep onset (sWASO), and total sleep time (sTST). Morning sleepiness/alertness, insomnia severity (Insomnia Severity Index [ISI]), fatigue (Fatigue Severity Scale [FSS]), perceptions of sleep-related medication effects (Patient Global Impression-Insomnia [PGI-I] questionnaire), and safety were also evaluated. In this subgroup of older adults (≥ 65years; n = 262), there were significantly larger changes from baseline for sSOL, sSE, sTST, and sWASO with LEM5 and LEM10 versus placebo through month 6 (except sWASO month 1), indicating improvement; these improvements were sustained through month 12. Subject-reported increases in morning alertness were significantly greater with one or both LEM doses versus placebo through month 6 and sustained through month 12. There were significantly larger ISI total and daytime functioning score decreases (improvement) from baseline with LEM versus placebo at months 1, 3, and 6 (total score: both doses; daytime functioning: LEM5 month 1 and both doses months 3 and 6) and decreases from baseline FSS at months 1 and 3 (LEM5) and month 6 (both doses), sustained to month 12. Compared with placebo, more subjects reported that LEM (both doses) positively impacted ability to sleep, time to fall asleep, and TST through month 6, sustained to month 12, with no rebound after drug withdrawal. LEM was well tolerated to month 12; mild somnolence was the most common treatment-emergent adverse event. Improvements in subject-reported efficacy in LEM-treated adults age ≥ 65years with insomnia were observed as early as the first week of treatment and sustained through end of month 12. LEM was well tolerated. ClinicalTrials.gov identifier NCT02952820: E2006-G000-303; Study 303; SUNRISE-2 (First posted: October 2016); EudraCT 2015-001463-39 (First posted: November 2016).

Managing the Patient with Psoriasis and Metabolic Comorbidities.

Epidemiological data demonstrate strong associations between psoriasis and metabolic comorbidities, including obesity, hypertension, diabetes mellitus, dyslipidemia, and non-alcoholic fatty liver disease. The presence of metabolic comorbidities significantly influences the selection and effectiveness of pharmacological treatments. Some drugs should be prescribed with caution in patients with metabolic comorbidities because of an increased risk of adverse events, while others could have a reduced effectiveness. The aim of this narrative review is to highlight the challenges that healthcare professionals may face regarding the management of psoriasis in patients with metabolic comorbidities. In the first part of the article, the epidemiological association between psoriasis and metabolic comorbidities and their pathogenetic mechanisms is summarized. The second part describes the efficacy and safety profile of conventional and biologic drugs in patients with selected metabolic comorbidities including obesity, non-alcoholic fatty liver disease/hepatic steatosis, and diabetes. Finally, the role of pharmacological and non-pharmacological interventions, such as diet, alcohol abstinence, physical activity, and smoking avoidance is discussed. In conclusion, the choice of the best approach to manage patients with psoriasis with metabolic comorbidities should encompass both tailored pharmacological and individualized non-pharmacological interventions.

Clinical Observations on the Combined Use of Hyperbaric Oxygenation and Conventional Medications in the Management of Type 2 Diabetes Mellitus Concurrent With Sudden Deafness.

Objective: The aim of this study is to investigate the effectiveness of combining hyperbaric oxygen therapy (HBOT) with conventional pharmacological interventions in the management of type 2 diabetes mellitus concurrent with sudden deafness. Methods: A cohort of 96 patients diagnosed with sudden deafness was enrolled and subsequently randomized into 2 groups: a treatment group (n = 50) and a control group (n = 46). The control group received standard conventional treatment aimed at enhancing microcirculation and nutritional support for nerves, while the treatment group underwent conventional symptomatic treatment coupled with HBOT. The evaluation encompassed the monitoring of blood glucose and blood lipid levels, clinical efficacy, and absolute hearing threshold improvement in both groups. Results: Following the intervention, noteworthy reductions in blood glucose and blood lipid levels were observed in both groups compared to their respective pretreatment values. Furthermore, posttreatment values in the treatment group exhibited a statistically significant decrease in comparison to those in the control group (P < .05). On assessing clinical efficacy posttreatment, the treatment group demonstrated a significantly higher efficacy than the control group (P < .05). In addition, the absolute hearing thresholds in both groups exhibited a significant decrease posttreatment compared to baseline values. Notably, the treatment group displayed a statistically significant reduction in absolute hearing thresholds compared to the control group posttreatment (P < .05). Conclusion: The combined therapeutic approach utilizing hyperbaric oxygen exhibits effectiveness in mitigating auditory impairment among individuals manifesting sudden deafness concomitant with type 2 diabetes mellitus. Furthermore, this treatment approach is associated with a concurrent reduction in blood glucose and blood lipid levels.

Sildenafil and furosemide nanoparticles as a novel pharmacological treatment for acute renal failure in rats.

Hospitalized patients often develop acute renal failure (ARF), which causes severe morbidity and death. This research investigates the potential renoprotective benefits of sildenafil and furosemide in glycerol-induced ARF, and measures kidney function metrics in response to nanoparticle versions of these medications. Inducing ARF is commonly done by injecting 50% glycerol intramuscularly. Rats underwent a 24-h period of dehydration and starvation before slaughter for renal function testing. We investigated urine analysis, markers of oxidative stress, histology of kidney tissue, immunohistochemistry analysis of caspase-3 and interleukin-1 beta (IL-1 β), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL), which are specific indicators of kidney tissue damage. The results of our study showed that the combination of sildenafil and furosemide, using both traditional and nanoparticle formulations, had a greater protective effect on the kidneys compared to using either drug alone. The recovery of renal tissue indicators, serum markers, and urine markers, which are indicative of organ damage, provides evidence of improvement. This was also indicated by the reduction in KIM-1 and NGAL tubular expression. The immunohistochemistry tests showed that the combination therapy, especially with the nanoforms, greatly improved the damaged cellular changes in the kidneys, as shown by higher levels of caspase-3 and IL-1β. According to the findings, a glycerol-induced rat model demonstrates that sildenafil and furosemide, either alone or in combination, in conventional or nanoparticulate forms, improve ARF dysfunction. The synergistic nanoparticulate compositions show remarkable effectiveness. This observation highlights the possible therapeutic implications for ARF treatment.

Challenges and pitfalls of youth-onset type 2 diabetes

The incidence and prevalence of youth-onset type 2 diabetes mellitus (T2DM) are increasing. The rise in frequency and severity of childhood obesity, inclination to sedentary lifestyle, and epigenetic risks related to prenatal hyperglycemia exposure are important drivers of the youth-onset T2DM epidemic and might as well be responsible for the early onset of diabetes complications. Indeed, youth-onset T2DM has a more extreme metabolic phenotype than adult-onset T2DM, with greater insulin resistance and more rapid deterioration of beta cell function. Therefore, intermediate complications such as microalbuminuria develop in late childhood or early adulthood, while end-stage complications develop in mid-life. Due to the lack of efficacy and safety data, several drugs available for the treatment of adults with T2DM have not been approved in youth, reducing the pharmacological treatment options. In this mini review, we will try to address the present challenges and pitfalls related to youth-onset T2DM and summarize the available interventions to mitigate the risk of microvascular and macrovascular complications.

Examining treatment targets and equity in bone-active medication use within secondary fracture prevention: a systematic review and meta-analysis.

This systematicreview seeks to evaluate the proportion of fragility fracture patients screened in secondary fracture prevention programs who were indicated for pharmacological treatment, received prescriptions for bone-active medications, and initiated the prescribed medication. Additionally, the study aims to analyze equity in pharmacological treatment by examining equity-related variables including age, sex, gender, race, education, income, and geographic location. We conducted a systematic review to ascertain the proportion of fragility fracture patients indicated for treatment who received prescriptions and/or initiated bone-active medication through secondary fracture prevention programs. We also examined treatment indications reported in studies and eligibility criteria to confirm patients who were eligible for treatment. To compute the pooled proportions for medication prescription and initiation, we carried out asingle group proportional meta-analysis. We also extracted the proportions of patients who received aprescription and/or began treatment based on age, sex, race, education, socioeconomic status, location, and chronic conditions. This review included 122 studies covering 114 programs. The pooled prescription rate was 77%, and the estimated medication initiation rate was 71%. Subgroup analysis revealed no significant difference in treatment initiation between the Fracture Liaison Service and other programs. Across all studies, age, sex, and socioeconomic status were the only equity variables reported in relation to treatment outcomes. Our systematic review emphasizes the need for standardized reporting guidelines in post-fracture interventions. Moreover, considering equity stratifiers in the analysis of health outcomes will help address inequities and improve the overall quality and reach of secondary fracture prevention programs.

Effects of pulmonary rehabilitation on functional and psychological parameters in post-acute sequelae of SARS-CoV-2 infection (PASC) patients

BackgroundCOVID-19 survivors may develop long-term symptoms of fatigue, dyspnea, mental health issues, and functional limitations: a condition termed post-acute sequelae of COVID-19 (PASC). Pulmonary rehabilitation (PR) is a recommended treatment for PASC; however, there is a lack of data regarding PR’s effect on multiple health indices and the factors that influence patient outcomes. The aim of our study is to evaluate the impact of pulmonary rehabilitation on functional and psychological parameters in patients diagnosed with Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), thereby offering insights into the efficacy of such interventions in improving the quality of life and clinical outcomes for these individuals.MethodsWe extracted patient demographic, comorbidity, and outcome data from Allegheny Health Network’s electronic medical records. Functionality test results were compared before and after PR, including 6-minute walk test (6MWT), chair rise repetitions (CR reps), timed up and go test (TUG), gait speed (Rehab gait), modified medical research council scale (MMRC), shortness of breath questionnaire (SOBQ), hospital anxiety and depression scale (HADS) and chronic obstructive pulmonary disease assessment test (CAT) scores. Multiple regression analysis was done to evaluate the effect of comorbidities and patient factors on patient responses to PR.ResultsThe 55 patients included in this study had a mean time of 4 months between the initial COVID-19 diagnosis and the subsequent PASC diagnosis. Following pulmonary rehabilitation (PR), significant improvements were observed across various metrics. The distance covered in the 6-minute walk test (6MWT) increased markedly from a pre-rehabilitation average of 895 feet (SD 290) to 1,300 feet (SD 335) post-rehabilitation, with a mean change of 405 feet (95% CI [333, 477]). Chair rise repetitions (CR reps) saw an increase from 9 (SD 3) reps to 13 (SD 3) reps, with a change of 4 reps (95% CI [3.7, 4.9]). The timed up and go test (TUG) time decreased significantly from 13 s (SD 5) to 10 s (SD 2), reflecting a mean reduction of 3 s (95% CI [-4.5, -2.5]). Rehabilitation gait speed improved from 1.0 m/s to 1.3 m/s, changing by 0.3 m/s (95% CI [0.2, 0.3]). The Modified Medical Research Council (MMRC) dyspnea scale showed a notable decrease from a mean of 2 (SD 1) to 1 (SD 1), a change of -1 (95% CI [-1.5, -1]). The Shortness of Breath Questionnaire (SOBQ) scores reduced significantly from 51 (SD 21) to 22 (SD 18), with a change of -29 (95% CI [-34, -23]). The Hospital Anxiety and Depression Scale (HADS) scores decreased from 11 (SD 7) to 8 (SD 7), a reduction of -4 (95% CI [-5, -2]). Lastly, the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) scores significantly dropped from 18 (SD 7) to 9 (SD 7), changing by -10 (95% CI [-11, -8]). However, the presence of hypertension, diabetes, chronic lung diseases, outpatient status, and receipt of specific pharmacologic treatments (decadron, decadron + remdesivir, and decadron + remdesivir + tocilizumab) were identified as factors associated with a poor response to PR.ConclusionOur study supports PR as an integrated model of care for PASC patients to improve several physical and mental health indices. The long-term effects of PR on patients’ functional status should be investigated in the future.

Inhibition of the morphological transition of Candida spp. by riparins I-IV.

Candida spp. is an opportunistic pathogen capable of causing superficial to invasive infections. Morphological transition is one of the main virulence factors of this genus and, therefore, is an important variable to be considered in pharmacological interventions. Riparins I, II, III, and IV are alkamide-type alkaloids extracted from the unripe fruit of Aniba riparia, whose remarkable pharmacological properties were previously demonstrated. This work aimed to evaluate in silico and in vitro the inhibitory effects of Riparins on the morphological transition of Candida albicans, Candida tropicalis, and Candida krusei. Molecular docking was applied to analyze the inhibitory effects of riparins against proteins such as N-acetylglucosamine, CYP-51, and protein kinase A (PKA) using the Ramachandran plot. The ligands were prepared by MarvinSketch and Spartan software version 14.0, and MolDock Score and Rerank Score were used to analyze the affinity of the compounds. In vitro analyses were performed by culturing the strains in humid chambers in the presence of riparins or fluconazole (FCZ). The morphology was observed through optical microscopy, and the size of the hyphae was determined using the ToupView software. In silico analysis demonstrated that all riparins are likely to interact with the molecular targets: GlcNAc (>50%), PKA (>60%), and CYP-51 (>70%). Accordingly, in vitro analysis showed that these compounds significantly inhibited the morphological transition of all Candida strains. In conclusion, this study demonstrated that riparins inhibit Candida morphological transition and, therefore, can be used to overcome the pathogenicity of this genus.

Transarterial microembolization for the management of refractory chronic joint pain in osteoarthritis.

Osteoarthritis (OA) is a chronic degenerative disease significantly impacting both patient quality of life and socioeconomics. Traditional treatment options, including pharmacological and surgical interventions, are often limited. Advancements in our understanding of the pathological mechanisms behind OA indicate the involvement of pathological angiogenesis. Transarterial microembolization (TAME), a minimally invasive radiological procedure, may present an innovative therapeutic approach. This review aims to consolidate current knowledge and experiences regarding TAME as a therapeutic modality for alleviating chronic joint pain associated with OA. It explores the role of TAME, focusing on its indications, patient selection, clinical outcomes, and future perspectives. Potential complications and associated risks are systematically addressed, alongside proposed strategies for risk mitigation and effective management.The presented patient cases originate from our institution, supplemented by a thorough review of relevant literature retrieved from PubMed.TAME represents a promising therapeutic approach, providing relief from the burden of joint diseases and substantially enhancing patient quality of life. Clinical outcomes emphasize the efficacy and safety of TAME in mitigating pain and improving functional capabilities in patients with chronic joint pain associated with OA. With mounting evidence of its therapeutic benefits and applicability to numerous joint-related pathologies, TAME offers a valuable addition to the arsenal of treatments for these conditions. · TAME is an innovative therapy for treating chronic joint pain related to OA.. · TAME is a technically challenging minimally invasive intervention requiring a high level of expertise.. · Understanding the challenges and complications of TAME can reduce risk and enhance procedural outcomes.. · Wilms LM, Jannusch K, Weiss D et al. Transarterial microembolization for the management of refractory chronic joint pain in osteoarthritis. Fortschr Röntgenstr 2024; DOI 10.1055/a-2288-5743.

Nurse independent prescribing: exploring the opportunities and challenges.

The Nursing and Midwifery Council states that nurses should be able to demonstrate competence in prescribing practice at the point of registration to be 'prescribing ready'. The aim is to increase the number of nurse independent prescribers and improve access to pharmacological treatments for patients. However, while this policy presents opportunities for nurses to develop their prescribing knowledge and skills, there are also challenges involved in integrating prescribing theory into nurse education and ensuring there are enough suitable mentors available in practice. This article details how the policy of prescribing readiness is being addressed in preregistration nurse education and explores the supervision of nurse prescribing in clinical practice. The author also discusses how best to support the professional development of nurse independent prescribers beyond their initial training.

A comprehensive review on the pharmacological role of gut microbiome in neurodegenerative disorders: potential therapeutic targets.

Neurological disorders, including Alzheimer and Parkinson's, pose significant challenges to public health due to their complex etiologies and limited treatment options. Recent advances in research have highlighted the intricate bidirectional communication between the gut microbiome and the central nervous system (CNS), revealing a potential therapeutic avenue for neurological disorders. Thus, this review aims to summarize the current understanding of the pharmacological role of gut microbiome in neurological disorders. Mounting evidence suggests that the gut microbiome plays a crucial role in modulating CNS function through various mechanisms, including the production of neurotransmitters, neuroactive metabolites, and immune system modulation. Dysbiosis, characterized by alterations in gut microbial composition and function, has been observed in many neurological disorders, indicating a potential causative or contributory role. Pharmacological interventions targeting the gut microbiome have emerged as promising therapeutic strategies for neurological disorders. Probiotics, prebiotics, antibiotics, and microbial metabolite-based interventions have shown beneficial effects in animal models and some human studies. These interventions aim to restore microbial homeostasis, enhance microbial diversity, and promote the production of beneficial metabolites. However, several challenges remain, including the need for standardized protocols, identification of specific microbial signatures associated with different neurological disorders, and understanding the precise mechanisms underlying gut-brain communication. Further research is necessary to unravel the intricate interactions between the gut microbiome and the CNS and to develop targeted pharmacological interventions for neurological disorders.

16S rRNA female reproductive microbiome investigation reveals Dalfopristin, Clorgyline, and Hydrazine as potential therapeutics for the treatment of bacterial vaginosis

Bacterial vaginosis (BV) is a prevalent vaginal illness resulting from a disruption in the vaginal microbial equilibrium. The vaginal microbiota has been shown to have a substantial impact on the development and continuation of BV. This work utilized 16S rRNA sequence analysis of vaginal microbiome samples (Control vs BV samples) utilizing Parallel-Meta 3 to investigate the variations in microbial composition. The unique genes identified were used to determine prospective therapeutic targets and their corresponding inhibitory ligands. Further, molecular docking was conducted and then MD simulations were carried out to confirm the docking outcomes. In the BV samples, we detected several anaerobic bacteria recognized for their ability to generate biofilms, namely Acetohalobium, Anaerolineaceae, Desulfobacteraceae, and others. Furthermore, we identified Dalfopristin, Clorgyline, and Hydrazine as potential therapeutic options for the management of BV. This research provides new insights into the causes of BV and shows the potential effectiveness of novel pharmacological treatments.

The topical azithromycin meibomian gland dysfunction survey: The effect of topical azithromycin on signs and symptoms of meibomian gland dysfunction.

The aim of this study was to assess the long-term effects of topical azithromycin on signs, symptoms and self-management of meibomian gland dysfunction (MGD). Forty participants were assessed for MGD and its effect on the fluorescein tear break-up time (FTBUT). Participants were treated with topical azithromycin twice daily for 2 weeks and then once daily for a further 2 weeks. One year after treatment, 31 participants completed a survey assessing pre- and post-treatment effect on symptoms, lifestyle and self-treatment methods. Following treatment, there was a significant reduction in MGD grading from a median of grade 2 to grade 0 (z = 4.40, p < 0.0001) and an increase in FTBUT from a median of 3-8 s (z = 4.75, p < 0.0001). One year afterwards, the survey showed a significant improvement in symptoms (sensitivity to light, grittiness, burning, blurred vision, all p < 0.03) and reduction in required self-treatments (lid wipes, tear substitutes, both p < 0.03). There was also a reduced impact on lifestyle (reading, night driving, computer use and watching television, all p < 0.0001) and in all environmental conditions (all p < 0.0001). This study confirms the positive effect of topical azithromycin on MGD and shows it has a long-term impact on symptoms, self-treatment methods and lifestyle. This has implications for both chair time and healthcare costs when managing patients with MGD. Pending further clinical trials in a larger population with different demographics, topical azithromycin should be considered by all eyecare practitioners as a viable pharmacological treatment when managing MGD.

Mechanisms of microbiota modulation: Implications for health, disease, and therapeutic interventions.

Microbiota modulation, the intentional change in the structure and function of the microbial community, is an emerging trajectory that holds the promise to mitigate an infinite number of health issues. The present review illustrates the underlying principles of microbiota modulation and the various applications of this fundamental process to human health, healthcare management, and pharmacologic interventions. Different strategies, directing on dietary interventions, fecal microbiota transplantation, treatment with antibiotics, bacteriophages, microbiome engineering, and modulation of the immune system, are described in detail. This therapeutic implication is reflected in clinical applications to gastrointestinal disorders and immune-mediated diseases for microbiota-modulating agents. In addition to this, the review outlines the challenges of translating researched outcomes into clinical practice to consider safety and provides insights into future research directions of this rapidly developing area.

Characteristics and management of juvenile type 2 diabetes mellitus

Background: Over the past two decades, there have been numerous reports on the increasing incidence of type 2 diabetes mellitus (T2DM) in children and adolescents. This trend, which parallels the increase in the prevalence and degree of pediatric obesity, is causing significant concern. This review focuses on the characteristics andcurrent management strategies for juvenile patients with T2DM. Current Concepts: Juvenile T2DM differs from type 1 diabetes mellitus (T1DM) in children and T2DM in adults as it is an aggressive disease with rapidly progressive β-cell decline, high treatment failure rate, and accelerated development of complications. Current management approaches include lifestyle changes such as improved diet and increased physical activity, and pharmacological interventions such as metformin, insulin, and liraglutide.Discussion and Conclusion: Early diagnosis and prevention of T2DM in children and adolescents are essential. Furthermore, compared to adults, there is still a lack of available treatment drugs or research in children and adolescents. Therefore, long-term research on the efficacy and safety of various drug treatments for T2DM in children and adolescents is required. Additionally, as it is often asymptomatic in its early stages, significant efforts by physicians are required for the early diagnosis and prevention of T2DM.

Experiences of schizophrenia patients with treatment buddy support during the COVID-19 pandemic

Background: Schizophrenia is a major psychiatric disorder affecting physical, psychosocial, and cognitive functioning. Treatment includes pharmacological and psychotherapeutic interventions. Adherence to prescribed medication is critical but reportedly low, because of side effects, failure to understand instructions, a lack of insight about the condition, cognitive deficits, and financial difficulties. Interventions to promote adherence to medication are required. This study introduced a treatment buddy to provide the patient with virtual support in adherence to medication.Aim: The aim of this study was to explore the participants’ lived experiences of a treatment buddy support.Setting: A specialised psychiatric clinic in a resource-constrained district of KwaZulu-Natal, South Africa.Methods: A qualitative study design, using semi-structured one-on-one interviews, was used to collect in-depth data from 24 participants, suffering from schizophrenia and who had been offered virtual treatment buddy support for 6 months. Data were analysed using thematic analysis.Results: The intervention improved adherence to medication. Participants indicated that the text messages served as reminders to take their medication daily. An alleviation of associated problems such as sleeping difficulties was observed. Participants were willing to encourage other patients suffering from schizophrenia to join ‘treatment buddy services’.Conclusion: The virtual treatment buddy support increased awareness of the importance to adhere to antipsychotic medications among patients suffering from schizophrenia and helped to resolve other schizophrenia-related problems experienced by the participants.Contribution: The study has provided a supportive intervention that can be utilised by mental health institutions to address poor adherence to medication by patients suffering from schizophrenia.

Lobetyolin protects mice against LPS-induced sepsis by downregulating the production of inflammatory cytokines in macrophage

Introduction: Sepsis is a clinical syndrome characterized by dysregulation of the host immune response due to infection, resulting in life-threatening organ damage. Despite active promotion and implementation of early preventative measures and bundle treatments, sepsis continues to exhibit high morbidity and mortality rates with no optimal pharmacological intervention available. Lobetyolin (LBT), the crucial component of polyacetylenes found in Codonopsis pilosula, has been scientifically proven to possess potent antioxidant and antitumor properties. However, its therapeutic potential for sepsis remains unknown.Methods: The mice received pretreatment with intraperitoneal injections of LBT, followed by injection with lipopolysaccharide (LPS) to induce sepsis. Peripheral blood samples were collected to detect TNF-α, IL-1β, and IL-6 levels. The survival status of different groups was recorded at various time intervals. RNA-Seq was utilized for the analysis of gene expression in peritoneal macrophages treated with LBT or LPS.Results: In this study, we observed a significant increase in the survival rate of mice pretreated with LBT in LPS induced sepsis mouse model. LBT demonstrated a remarkable reduction in the production of IL-6, TNF-α, and IL-1β in the serum, along with mitigated lung and liver tissue damage characterized by reduced inflammatory cell infiltration. Additionally, through RNA-seq analysis coupled with GO and KEGG analysis, it was revealed that LBT effectively suppressed genes associated with bacterium presence, cellular response to lipopolysaccharide stimulation, as well as cytokine-cytokine receptor interaction involving Cxcl10, Tgtp1, Gbp5, Tnf, Il1b and IRF7 specifically within macrophages. We also confirmed that LBT significantly downregulates the expression of IL-6, TNF-α, and IL-1β in macrophage activation induced by LPS.Discussion: Therefore, our findings demonstrated that LBT effectively inhibits the production of inflammatory cytokines (IL-6, TNF-α, and IL-1β) and mitigates sepsis induced by LPS through modulating macrophages' ability to generate these cytokines. These results suggest that LBT holds promise as a potential therapeutic agent for sepsis treatment.

PML restrains p53 activity and cellular senescence in clear cell renal cell carcinoma.

Clear-cell renal cell carcinoma (ccRCC), the major subtype of RCC, is frequently diagnosed at late/metastatic stage with 13% 5-year disease-free survival. Functional inactivation of the wild-type p53 protein is implicated in ccRCC therapy resistance, but the detailed mechanisms of p53 malfunction are still poorly characterized. Thus, a better understanding of the mechanisms of disease progression and therapy resistance is required. Here, we report a novel ccRCC dependence on the promyelocytic leukemia (PML) protein. We show that PML is overexpressed in ccRCC and that PML depletion inhibits cell proliferation and relieves pathologic features of anaplastic disease in vivo. Mechanistically, PML loss unleashed p53-dependent cellular senescence thus depicting a novel regulatory axis to limit p53 activity and senescence in ccRCC. Treatment with the FDA-approved PML inhibitor arsenic trioxide induced PML degradation and p53 accumulation and inhibited ccRCC expansion in vitro and in vivo. Therefore, by defining non-oncogene addiction to the PML gene, our work uncovers a novel ccRCC vulnerability and lays the foundation for repurposing an available pharmacological intervention to restore p53 function and chemosensitivity.

POST-OPERATIVE PROTOCOL FOR BRAIN TUMOR SURGERY IN INTENSIVE CARE UNIT: A LITERATURE REVIEW

Background: Brain tumors represent a diverse group of neoplasms arising from intracranial tissues, posing significant clinical challenges and impacting public health globally. With primary brain tumors having an annual incidence of around 14 per 100,000 individuals and secondary brain tumors being even more prevalent, the burden on healthcare systems is substantial. Postoperative care, particularly in the intensive care unit (ICU), plays a crucial role in monitoring patients for early detection of complications and maintaining neurological and systemic homeostasis. This study aims to serve a literature review to examine post operative management in brain surgery operation in the ICU in literatures. Result and Discussion: Protocols for ICU management post-brain tumor surgery are essential, with factors such as patient status, surgical site, and anticipated postoperative needs guiding decisions regarding ICU admission and monitoring. Neuroprotective strategies encompass physiological and pharmacological interventions aimed at mitigating adverse outcomes, with a multifaceted approach necessary for optimal neuroprotection. Conclusion: A comprehensive understanding of the surgical and postoperative management of brain tumors along with the implementation of evidence-based protocols for ICU care are essential to improve patient outcomes and minimize complications. Continued advancements in surgical techniques, neuroprotective strategies, and critical care management are crucial in addressing the complex challenges posed by brain tumors and enhancing the quality of care for affected patients.

Correlation of TRPA1 RNAscope and Agonist Responses.

The TRPA1 ion channel is a sensitive detector of reactive chemicals, found primarily on sensory neurons. The phenotype exhibited by mice lacking TRPA1 suggests its potential as a target for pharmacological intervention. Antibody-based detection for distribution analysis is a standard technique. In the case of TRPA1, however, there is no antibody with a plausible validation in knockout animals or functional studies, but many that have failed in this regard. To this end we employed the single molecule in situ hybridization technique RNAscope on sensory neurons immediately after detection of calcium responses to the TRPA1 agonist allyl isothiocyanate. There is a clearly positive correlation between TRPA1 calcium imaging and RNAscope detection (R = 0.43), although less than what might have been expected. Thus, the technique of choice should be carefully considered to suit the research question. The marginal correlation between TRPV1 RNAscope and the specific agonist capsaicin indicates that such validation is advisable for every RNAscope target. Given the recent description of a long-awaited TRPA1 reporter mouse, TRPA1 RNAscope detection might still have its use cases, for detection of RNA at particular sites, for example, defined structurally or by other molecular markers.