Drug Therapy Research Articles

Stromal CD73 Expression in Breast Cancer: Subtype-specific Expression and its Prognostic Significance.

Invasive ductal carcinoma (IDC) is classified into distinct subtypes with varying prognoses and treatment sensitivities. For instance, triple-negative breast cancer (TNBC) is associated with poorer outcomes than other subtypes. We have previously reported the role of interstitial CD73 in tumor invasion and its correlation with prognosis in other cancers. This study aimed to investigate the expression of stromal CD73 (sCD73) in IDC and its potential prognostic significance. We analyzed 61 cases of human epidermal growth factor receptor 2-negative IDC, including TNBC and hormone receptor-positive (luminal-type) cases, treated surgically at our institution from 2005 to 2010. Cases that received preoperative drug therapy were excluded. CD73 expression was evaluated by immunostaining of the tumor stroma. sCD73 expression was observed in 70% of all cases, with a significantly higher rate in TNBC (93%) compared with luminal breast cancer (48%). High sCD73 expression was associated with poor prognosis in terms of overall survival (OS) and disease-free survival (DFS) across all cases. In patients with luminal breast cancer, high sCD73 expression was also indicative of poor prognosis with respect to both OS and DFS. High expression of sCD73 is associated with poor prognosis in IDC, particularly in luminal breast cancer. Further research is needed to establish sCD73 as an independent prognostic factor.

Several orphan solute carriers functionally identified as organic cation transporters: Substrates specificity compared with known cation transporters

Organic cations comprise a significant part of medically relevant drugs and endogenous substances. Such substances need organic cation transporters (OCT) for efficient transfer via cell membranes. However, the membrane transporters of most natural or synthetic organic cations the membrane transporters are still unknown. To identify these transporters, genes of 10 known OCTs and 18 orphan solute carriers (SLC) were overexpressed in HEK293 cells and characterized concerning their transport activities with a broad spectrum of low molecular weight substances emphasizing organic cations. Several SLC35 transporters and SLC38A10 significantly enhanced the transport of numerous relatively hydrophobic organic cations. Significant organic cation transport activities have been found in gene families classified as transporters of other substance classes. For instance, SLC35G3 and SLC38A10 significantly accelerated the uptake of several cations, such as clonidine, 3,4-methylenedioxymethamphetamine, and nicotine, which are known as substrates of a thus far genetically unidentified proton/organic cation antiporter. The transporters SLC35G4 and SLC35F5 stood out by their significantly increased choline uptake, and several other SLC transported choline together with a broader spectrum of organic cations. Overall, there are many more polyspecific organic cation transporters than previously estimated. Several transporters had one predominant substrate but accepted some other cationic substrates, and others showed no particular preference for one substrate but transported several organic cations. The role of these transporters in biology and drug therapy remains to be elucidated.

Uterine fibroids: current research on novel drug targets and innovative therapeutic strategies.

Uterine fibroids, the most common nonmalignant tumors affecting the female genital tract, are a significant medical challenge. This article focuses on the most recent studies that attempted to identify novel non-hormonal therapeutic targets and strategies in UF therapy. This review covers the analysis of the pharmacological and biological mechanisms of the action of natural substances and the role of the microbiome in reference to UFs. This study aimed to determine the potential role of these compounds in UF prevention and therapy. While there are numerous approaches for treating UFs, available drug therapies for disease control have not been optimized yet. This review highlights the biological potential of vitamin D, EGCG and other natural compounds, as well as the microbiome, as promising alternatives in UF management and prevention. Although these substances have been quite well analyzed in this area, we still recommend conducting further studies, particularly randomized ones, in the field of therapy with these compounds or probiotics. Alternatively, as the quality of data continues to improve, we propose the consideration of their integration into clinical practice, in alignment with the patient's preferences and consent.

Ameliorating Gonorrhea: Recent Therapeutic Adaptations and Scope to Improve its Prevailing Condition.

Gonorrhea is a sexually transmitted infection (STI) caused by the bacteria Neisseria gonorrhoeae. According to recent research, the prevalence of gonorrhea has been increasing in many parts of the world, with some areas reporting high rates of antibiotic resistance. In the United States, the Centers for Disease Control and Prevention (CDC) reported that the number of reported gonorrhea cases increased by 56% between 2015 and 2019. Globally, the World Health Organization (WHO) estimated that there were 87 million new cases of gonorrhea in 2016, with the highest burden of infection in low- and middle-income countries. Research has also shown that gonorrhea is becoming increasingly resistant to conventional antibiotics, increasing the prevalence of gonorrhea. This raises concerns and challenges in disease management. The present review gives updated insight on the current state of the disease, challenges, and shortcomings of existing approaches along with the modern and alternative direction like vaccine development, its challenges, and scope to confront the existing state of drug resistance and increased rate of incidence. Alternative strategies like immunotherapy and phage therapy along with recent antibiotics researched for the treatment of gonorrhea. The review provides a thorough insight into the current state of the disease and various available methods used currently and recommended by WHO. To overcome disease prevalence, various alternate therapies are coming into the limelight. However, scientists and researchers show a lack of interest in the drug development and research of gonorrhea, due to less commercial scope, lack of funding, and limited scope in the scientific scenario. These hurdles need to be overcome to meet the WHO vision of reducing gonorrhea by 90% by 2030. So, there is a need to optimize the drug therapy (optimizing dosing schedule, and precision monitoring) to reduce the chance of drug resistance. Also, there is a wide scope for drug and therapeutic system development.

Effect of inhalation drug therapy on inflammatory factors and quality of life on stable chronic obstructive pulmonary disease.

To investigate the clinical efficacy of inhaled triple therapy in the treatment of stable chronic obstructive pulmonary disease (COPD). This is a clinical comparative study. A total of 80 patients with COPD admitted to the First People's Hospital of Suining City from June 2020 to June 2023 were included and randomly divided into the study (conventional COPD treatment + inhaled triple therapy) and control (conventional COPD treatment) groups. The clinical efficacy of inhaled triple therapy and adverse reactions of the two groups to the treatment were observed. Clinical efficacy was assessed through changes in pulmonary function indexes, and comparisons of T lymphocyte subsets and serum inflammatory markers were conducted. In addition, St George's Respiratory Questionnaire (SGRQ) was employed for the quality-of-life assessment. The study group showed a significantly higher total efficacy than the control group (P < 0.05), with no significant difference in terms of adverse reactions between them (P > 0.05). After treatment, the study group showed better improvement in pulmonary function indexes, such as forced expiratory volume in one second (FEV1), FEV1 as a percentage of the expected value, forced vital capacity (FVC) and FEV1/FVC, compared with the control group (all P < 0.05). In addition, the study group presented higher levels of T lymphocyte subsets CD3+, CD4+ and CD4+/CD8+ than the control group(all P < 0.05). After treatment, the levels of inflammatory markers tumour necrosis factor-α, leukotriene B4 LTB4 and interleukin-6 in the study group decreased more than those in the control group (all P < 0.05). Moreover, the study group attained a lower SGRQ score than the control group (all P < 0.05). Triple inhalants further improve the clinical efficacy of the treatment of COPD.

Chinese guidelines for integrated diagnosis and treatment of intestinal microecology technologies in tumor application (2024 Edition).

Intestinal microecology (IM) is the largest and most important microecological system of the human body. Furthermore, it is the key factor for activating and maintaining the physiological functions of the intestine. Numerous studies have investigated the effects of the gut microbiota on the different tissues and organs of the human body as well as their association with various diseases, and the findings are gradually being translated into clinical practice. The gut microbiota affects the occurrence, progression, treatment response, and toxic side effects of tumors. The deepening of research related to IM and tumors has opened a new chapter in IM research driven by methods and technologies such as second-generation sequencing and bioinformatics. The IM maintains the function of the host immune system and plays a pivotal role in tumor-control drug therapy. Increasing evidence has proven that the efficacy of tumor-control drugs largely depends on the IM balance, and strategies based on the IM technology show promising application prospects in the diagnosis and treatment of tumor. The Tumor and Microecology Professional Committee of the Chinese Anti-cancer Association gathered relevant experts to discuss and propose the "Chinese guidelines for integrated diagnosis and treatment of IM technologies in tumor application (2024 Edition)," which was established based on the research progress of the application of the IM technology in tumor to provide a basis for the standardization of the diagnosis and treatment of the IM technology in the tumor.

Integrated network pharmacology and molecular docking to investigate the potential mechanism of Tufuling on Alzheimer's disease

ObjectiveThis study aimed to investigate the mechanism of Tu Fu Ling in treating Alzheimer's disease (AD) using network pharmacology and molecular docking. MethodsThe TCMSP and Swiss target prediction databases were utilized to confirm the active components of Tu Fu Ling and their corresponding targets, with target gene names converted using the UniProt database. Genes related to AD were collected from DisGeNET, GeneCards, and the Open Target Platform databases. Common target genes between the disease and the drug were obtained using Venny 2.1 tools and visualized using Cytoscape software. Protein-protein interaction (PPI) data were further analyzed to determine correlations between common target genes, and GO and KEGG pathway enrichment analyses were performed for intersecting genes. Finally, PYmol, AutoDock Tool, Discovery Studio 2020, and PyRx software were used for preliminary computer virtual verification and visualization of active drug ingredients and target proteins. ResultsNine active ingredients meeting the screening criteria yielded a total of 168 genes after removing duplicates. A total of 3833 target genes were collected, with 129 overlapping target genes identified. GO enrichment analysis identified 643 biological processes, 82 cellular components, and 147 molecular functions. KEGG pathway enrichment analysis also revealed a pathway closely related to AD (hsa05010: Alzheimer's disease). In molecular docking analysis, the binding affinity between the 9 active ingredients and 10 core targets ranged from −3.5 to −12.3 kcal/mol, indicating strong binding. ConclusionThis study preliminarily verified the combination of Tu Fu Ling's screened active ingredient and the calculated core target, suggesting a potential mechanism of action to improve the symptoms of AD patients through multi-target and multi-pathway approaches. This provides a valuable reference for further exploration of the pharmacological mechanism of AD and the formulation of drug therapy.

Fluspirilene exerts an anti-glioblastoma effect through suppression of the FOXM1-KIF20A axis.

Given the infiltrative nature of human glioblastoma (GBM), cocktail drug therapy will remain a vital tool for the treatment of the disease. We investigated fluspirilene, perphenazine, and sulpiride, three classic anti-schizophrenic drugs, as possible anti-GBM agents. The CCK-8 assay demonstrated that fluspirilene possesses the most outstanding anti-GBM effect. We performed molecular mechanisms studies in vitro and an orthotopic xenograft model in mice. Fluspirilene inhibited proliferation and migration in vitro in U87MG and U251 GBM cell lines. Flow cytometry demonstrated that treatment increased apoptosis and cells accumulated in the G2/M phase. Our analysis of publicly available expression data for several cell lines treated with the drug led to the identification of several genes, including KIF20A, that are downregulated by fluspirilene and lead to growth inhibition/apoptosis. We also demonstrated that siRNA knockdown of KIF20A, a member of the kinesin family, attenuated cell proliferation in GBM cells and an orthotopic xenograft model in mice. A regulator of KIF20A, the oncogenic transcription factor FOXM1, was identified using the String database, which harbors protein interaction networks. In fluspirilene-treated cells, FOXM1 protein was decreased, indicating that KIF20A was downregulated in the presence of the drug due to decreased FOXM1 protein. These results demonstrate that fluspirilene is an effective anti-GBM agent that works by suppressing the FOXM1-KIF20A oncogenic axis.

Neoadjuvant Versus Adjuvant Systemic Therapy in Breast Cancer: A Matched Case-control Study.

Neoadjuvant systemic therapy (NAT) in breast cancer can make tumors resectable or reduce the extent of surgery needed for locally advanced cancers. It can also better prevent distant relapse and possibly modulate drug therapy by adjusting adjuvant therapy (AD) based on the response to NAT, either by escalating or de-escalating the treatment. However, clear evidence of improved outcomes is currently missing. Here, we report on breast cancer patients treated with NAT at our institution. One hundred twenty-seven patients treated at our Radiation Oncology department between 2004 and 2021 were retrospectively analyzed. All patients had localized or locally advanced breast cancer, were treated with NAT, and received postoperative radiotherapy. The outcomes considered were overall survival (OS), loco-regional recurrence-free survival (LRRFS), and distant metastases-free survival (DMFS). A matched patient population treated with AD during the same period and at the same center was used for comparison. The 5-year predicted OS was 87% in the NAT group and 81.5% in the AD group (p-value=0.179), while LRRFS was 93.2% in the NAT group and 100% in the AD group (p=0.005). The 5-year predicted DMFS was 84.6% in the NAT group and 82.1% in AD patients (p=0.367). In the NAT group, the only prognostic factor significantly related to improved outcomes was the pathological node response, with an OS of 95.6% in patients without residual node disease compared to 75.1% in patients with evidence of residual node disease. Our study, despite the limitations of a small number of patients and its retrospective nature, confirms the data of previous larger studies. In terms of DMFS and OS, NAT is at least as effective as AD. NAT represents a great opportunity for personalized modulation of treatment in node-positive breast cancer patients.

The current state of the problem, clinical-pathogenetic approaches to the diagnosis and management tactics of fetal growth restriction

Fetal growth restriction is a common complication of pregnancy with a complex etiology and limited possibilities of diagnosis and treatment. The relevance of this difficult obstetric problem is determined by various published diagnostic criteria, relatively low detection rates, and limited options for prevention and treatment.Fetal growth restriction is defined as the inability of the fetus to reach its genetically determined growth potential, most often due to abnormal placentation. Forms of fetal growth restriction with early or late onset are distinguished based on the gestational age determined during prenatal ultrasound diagnosis. According to most recommendations, the 32nd week of pregnancy is set as the cut-off point for distinguishing between early and late onset fetal growth restriction.The definition underlying this classification is based on differences between these two phenotypes of fetal growth restriction in severity, natural history, Doppler findings, association with hypertensive complications, placental features, and management. It is important to distinguish two separate conditions: fetal growth restriction and small-for-gestational fetus, which differ in short-term and long-term perinatal outcomes.A fetus is defined as small for gestational age if the estimated weight or weight of the fetus at birth is below the 10th percentile. Fetal growth restriction is diagnosed if the estimated fetal weight is below the 3rd percentile or a combination of pathological blood flow in the umbilical arteries and/or uterine arteries in fetuses with an estimated weight below the 10th percentile. It can also occur in fetuses and newborns with a body weight above the 10th percentile.The need to distinguish between fetal growth restriction and small-for-gestational-age fetus is related to the fact that fetal growth restriction is the main cause of stillbirth, neonatal death, higher perinatal morbidity, as well as increased risk of diseases in adulthood.The article analyzes the approaches to differentiating fetal growth restriction from small growth retardation in terms of fetal gestation period and further increasing the accuracy of diagnosis, as well as the modern concept of pathogenesis, with an emphasis on oxidant stress as a key molecular mechanism of adverse outcomes. Appropriate interventions during pregnancy to reduce perinatal complications should include antenatal monitoring and drug therapy.

FLORES: VERDADEIRO RESERVATÓRIO DE ANTIBIÓTICOS E RESINAS ANTIMICROBIANAS

Microbial resistance is the versatility of microorganisms not to succumb to the harsh environment and to maintain themselves in all environmental compartments, organisms and living cells. This phenomenon is a mechanism of acquired adaptation that directly impacts humans and animals, as these organisms have disharmonious relationships with them, causing several practically intractable pathologies, leading to the death of the host. The World Health Organization points out, every year, the increase of microorganisms resistant to drugs, both for domestic and hospital use, publishing in its reports, the frightening reality of organisms resistant to all commercialized drugs, being called Pan-resistant. Therefore, the objective of the study is to investigate in fresh, freshly picked flowers, a new substance with antimicrobial and/or bactericidal power against Enterobacteria. Of the 66 flowers studied, 29 showed some promising antibiotic/bactericidal effect, with passion fruit and mallow being the ones that stood out the most, followed by dahlia and munguba. The hexane extract of the passion fruit flower showed a halo of formation greater than Gentamicin and Amikacin, of 22 mm with only 0.5 g of the flower. Several studies describe the complexity of substances found in passion fruit flower, making it difficult to indicate a possible organic group or the combination of mixed organic compounds with synergistic effects. The mallow flower, which has the coumarin malvina and the terpenoid malvona exclusively, presented an inhibition halo comparable to antibiotic discs already used in drug therapies, with an effect on all three Enterobacteriaceae studied, Salmonella serotype thyphimurium NCTC® 12023, multiresistant Escherichia coli, and the pan-resistant bacterium kpcKlebsiella planticola2019, being a great antimicrobial potential. For a similar bacteriostatic effect of propolis, 22 flowers expressed a glutinous, expansive and resinous effect, in order to immobilize and prevent an aggressive and pathogenic agent from expressing its metabolism or life cycle, with the highlight being azalea, presenting the largest halo.Thus, it is possible to infer that the production of propolis by bees is the sum of the harvesting of resins from several species of flowers, both exotic and native, in the manufacture of the best resin to protect their hives. Finally, the trend of phytotherapy combined with modern biotechnological science may be the key to success against highly specialized parasites. This study falls under SDG 13 (quality health) and SDG 15 (life on land) of the development goals.

Local Allergic Rhinitis-A Challenge for Allergology and Otorhinolaryngology Cooperation (Scoping Review).

Local allergic rhinitis (LAR) represents a medical provocation for allergists and otorhinolaryngologists. LAR is considered to be a subtype of allergic rhinitis (AR) that affects a great percentage of patients who were, for decades, diagnosed as having chronic non-allergic rhinitis. The clinical picture is represented by rhinorrhea, sneezing, and nasal itching correlated with specific pollen season or dust, mold, or pet interior exposure. Usual assessment of AR (skin prick testing and serum IgE assessment) produces negative results. Specialized centers in allergology and ENT around the globe use a nasal allergen challenge, assessment of local IgE, basophil activation test (BAT), and nasal cytology in the diagnostic approach to the disease, taking into account their current limitations. The impact of LAR on quality-of-life indicators is the same as in AR. Treatment for LAR is similar to that for AR and is the same as for AR: allergen exposure avoidance, drug therapy, and allergen immunotherapy. This scoping review gathers the current up-to-date open access evidence available on PubMed on the subject of LAR.

Single and combined strategies for mesenchymal stem cell exosomes alleviate liver fibrosis: a systematic review and meta-analysis of preclinical animal models.

Background: The efficacy of mesenchymal stem cells (MSCs) in treating liver fibrosis has been supported by various clinical studies. However, stem cell transplantation is limited in clinical application due to its low survival rate, low liver implantation rate, and possible carcinogenicity. Recently, there has been increasing interest in the use of MSC-exos due to their widespread availability, low immunogenicity, and non-carcinogenic properties. Numerous studies have demonstrated the potential of MSC-exos in treating liver fibrosis and preventing progression to end-stage liver disease. Objective: This study aimed to systematically investigate the efficacy of MSC-exos single administration in the treatment of hepatic fibrosis and the combined advantages of MSC-exos in combination with drug therapy (MSC-exos-drugs). Methods: Data sources included PubMed, Web of Science, Embase, and the Cochrane Library, which were built up to January 2024. The population, intervention, comparison, outcomes, and study design (PICOS) principle was used to screen the literature, and the quality of the literature was evaluated to assess the risk of bias. Finally, the data from each study's outcome indicators were extracted for a combined analysis. Results: After screening, a total of 18 papers (19 studies) were included, of which 12 involved MSC-exos single administration for the treatment of liver fibrosis and 6 involved MSC-exos-drugs for the treatment of liver fibrosis. Pooled analysis revealed that MSC-exos significantly improved liver function, promoted the repair of damaged liver tissue, and slowed the progression of hepatic fibrosis and that MSC-exos-drugs were more efficacious than MSC-exos single administration. Subgroup analyses revealed that the use of AD-MSC-exos resulted in more consistent and significant efficacy when MSC-exos was used to treat hepatic fibrosis. For MSC-exos-drugs, a more stable end result is obtained by kit extraction. Similarly, infusion through the abdominal cavity is more effective. Conclusion: The results suggest that MSC-exos can effectively treat liver fibrosis and that MSC-exos-drugs are more effective than MSC-exos single administration. Although the results of the subgroup analyses provide recommendations for clinical treatment, a large number of high-quality experimental validations are still needed. Systematic Review Registration: CRD42024516199.

Development of Organ Targeting Lipid Nanoparticles with Low Immunogenicity and Its Application in the Treatment of Pulmonary Fibrosis

As the most advanced non‐viral delivery system, lipid nanoparticles (LNPs) were approved by the FDA, propelling the advancements of gene therapy. However, their clinical applications are hampered by the potential immunogenicity of the lipid components that trigger immune‐related adverse events, like inflammation and allergy. Herein, we formulate various dLNPs with diminished immunogenicity by incorporating dexamethasone (Dex) into liver‐, spleen‐, and lung‐targeting LNPs formulations that exhibit excellent abilities to target specific organs and deliver various types of RNA, such as mRNA and siRNA. In vivo investigations demonstrate unparalleled advantages in safety compared to conventional LNPs, showing promising potential in the development of RNA therapeutics. Intriguingly, the encapsulation of runt‐related transcription factor‐1 siRNA (siRUNX1) into lung‐targeting dLNPs (dLNPs@siRUNX1) demonstrates remarkable advantages in the treatment of pulmonary fibrosis through the synergy of gene therapy and drug therapy. This research establishes secure and universal platforms for the precise delivery of nucleic acid therapeutics, showcasing promising clinical applications in gene therapy.

PREVENTION AND TREATMENT OF POSTOPERATIVE INFECTIONS IN IMPACTED THIRD MOLAR SURGERIES

repair are examined, highlighting the importance of the blood clot and its adverse effects, from its malformation to its loss. The study covers risk factors, diagnosis, symptoms and prevention of these complications, emphasizing that infections can manifest up to 30 days after surgery. Although uncommon, these infections are seen as the main reason for delayed healing after surgery. The classification of third molar removal surgery as contamination is debated in relation to the incidence of infections, highlighting the importance of care and operative technique compared to the prophylactic administration of antibiotics. Specific guidelines are demonstrated for patients with compromised immune systems. The content develops prevention strategies, including decontamination, use of sterile materials, drug therapy, cleaning and debridement of surgical wounds in order to treat and prevent such infections. It stresses that the use of antibiotics is not justified by the absence of biosafety precautions and emphasizes the essentiality of maintaining the aseptic chain for successful treatment. This research aims to contribute to a more in-depth understanding of post-operative complications in third molar extractions, providing a preventative and effective approach to dental surgery.

Development of Organ Targeting Lipid Nanoparticles with Low Immunogenicity and Its Application in the Treatment of Pulmonary Fibrosis.

As the most advanced non-viral delivery system, lipid nanoparticles (LNPs) were approved by the FDA, propelling the advancements of gene therapy. However, their clinical applications are hampered by the potential immunogenicity of the lipid components that trigger immune-related adverse events, like inflammation and allergy. Herein, we formulate various dLNPs with diminished immunogenicity by incorporating dexamethasone (Dex) into liver-, spleen-, and lung-targeting LNPs formulations that exhibit excellent abilities to target specific organs and deliver various types of RNA, such as mRNA and siRNA. In vivo investigations demonstrate unparalleled advantages in safety compared to conventional LNPs, showing promising potential in the development of RNA therapeutics. Intriguingly, the encapsulation of runt-related transcription factor-1 siRNA (siRUNX1) into lung-targeting dLNPs (dLNPs@siRUNX1) demonstrates remarkable advantages in the treatment of pulmonary fibrosis through the synergy of gene therapy and drug therapy. This research establishes secure and universal platforms for the precise delivery of nucleic acid therapeutics, showcasing promising clinical applications in gene therapy.

Benefit assessment of novel systemic therapies for bone and soft tissue sarcomas: a cross-sectional study.

Bone and soft tissue sarcomas are rare malignancies, and their heterogeneity has limited the development of novel drugs. This study aimed to apply two validated tools to evaluate the clinical benefits of novel drug therapies for sarcoma developed over the last decade. The PubMed and Embase databases were searched for randomized controlled trials (RCTs) of systemic therapies for sarcomas published between 2013 and 2023. Each trial was scored according to the European Society of Medical Oncology-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS) and the American Society of Clinical Oncology-Value Framework version 2 (ASCO-VF). We included 52 RCTs in this study, of which 17 (32.7%) reported positive results that favored the experimental arm. The ESMO-MCBS grades were determined in 14/17 positive trials, and three of them (21.4%) met the threshold for meaningful clinical benefit. Likewise, ASCO-VF scores were calculated for 11/17 positive trials, and three of them (27.3%) met the threshold for meaningful clinical benefit. Weak correlation (r = 0.38, P = 0.277) and agreement (κ = 0.211, P = 0.490) were observed between the two frameworks. Only a few RCTs with positive results have demonstrated substantial patient benefits for bone and soft tissue sarcomas over the past decade.

Effect of a single pill concept on clinical and pharmacoeconomic outcomes in cardiovascular diseases.

Our study aimed to assess whether a single pill concept (SPC) is superior to a multi pill concept (MPC) in reducing cardiovascular (CV) events, all-cause death, and costs in CV patients. Anonymized medical claims data covering 2012-2018, including patients with hypertension, dyslipidemia, and CV diseases who started a drug therapy either as SPC or identical MPC were analyzed after 1:1-Propensity Score Matching (PSM). Hospitalizations with predefined CV events, all-cause mortality, and costs were studied in 25,311 patients with SPC and 25,311 patients with MPC using incidence rate ratios (IRRs) and non-parametric tests for continuous variables.IRRs were significantly lower for SPC: stroke (IRR=0.77; 95% CI 0.67-0.88; p<0.001), transitory ischemic attack (IRR=0.61; 95% CI 0.48-0.78; p<0.001), myocardial infarction (IRR=0.76; 95% CI 0.63-0.90; p=0.0016), coronary artery disease (IRR=0.66; 95% CI 0.57-0.77; p<0.001), heart failure (IRR=0.59; 95% CI 0.54-0.64; p<0.001), acute renal failure (IRR=0.54; 95% CI 0.56-0.64; p<0.001), all cause hospitalization (IRR=0.72; 95% CI 0.71-0.74; p<0.001), CV hospitalization (IRR=0.63; 95% CI 0.57-0.69; p<0.001), and all-cause mortality (IRR=0.62; 95% CI 0.57-0.68; p<0.001). Mean time to first events and time to death were also in favor of SPC. Mean total costs were 4,708 € for SPC vs. 5.669 € for MPC, respectively (MR 0.830, p<0.001). SPC is associated with lower incidence rates of CV events, time to CV events, and all-cause death, and is superior regarding pharmacoeconomic parameters and should therefore become standard of care to improve outcomes and reduce healthcare costs.

Salmonella Typhimurium alters galactitol metabolism under ciprofloxacin treatment to balance resistance and virulence.

Treatment of antibiotic resistance can significantly benefit from a deeper understanding of the interactions between drugs and genetics. The physiological responses and genetic mechanisms in antibiotic-exposed bacteria are not well understood. Traditional resistance studies, often retrospective, fail to capture the entire resistance development process and typically exhibit unpredictable dynamics. To explore how clinical isolates of S. Typhimurium respond to ciprofloxacin, we analyzed their adaptive responses. We found that S. Typhimurium RamA-mediated regulation disrupts microbial metabolism under ciprofloxacin exposure, affecting genes in the galactitol metabolic pathways. This disruption facilitates adaptive responses to drug therapy and enhances the efficiency of intracellular survival. A more comprehensive and integrated understanding of these physiological and genetic changes is crucial for improving treatment outcomes.

Advances in medications and treatments for reducing memory loss in Alzheimer's disease

Alzheimer's disease (ad) is a disease in which brain cells deteriorate, leading to dementia and cognitive decline. It is mainly caused by cholinergic functional problems and the accumulation of amyloid plaques in the brain. Age, genetics, head damage, vascular disease, infection and environmental factors can also cause the disease. Currently, only two drugs have been approved for the treatment of Alzheimers disease, but they only target symptoms and cannot cure or prevent the disease. Ongoing research aims to better understand Alzheimers disease and develop treatments that can slow or change its progress in response to mechanisms such as beta-amyloid plaques, inflammation and cholinergic dysfunction with abnormal tau metabolism. The focus of this review is on current drug therapy and the causes of Alzheimers disease, including those that change the disease, as a partner, or use natural compounds.