Significant Side Effects Research Articles

Systemic Treatment With Cyclosporine A in Children With Severe Vernal Keratoconjunctivitis.

To report our experience with systemic cyclosporine as a treatment for severe vernal keratoconjunctivitis (VKC) in pediatric patients who did not respond to previous treatments. We analyzed the medical records of 6 patients, aged 4 to 15 years, with severe VKC treated with systemic cyclosporine for VKC at Shamir Medical Center in Zerifin, Israel, between the years 2000 and 2023. The average treatment duration was 18 months. In all patients, previous treatments with antihistamines, mast cells stabilizers, topical steroids and topical cyclosporine, and systemic steroids did not result in sufficient improvement. The severity of inflammation was evaluated during clinical examinations and the patients' subjective assessment of their quality of life. In all 6 patients, signs and symptoms showed significant improvement within 2 to 4 weeks of initiating systemic cyclosporine treatment. All patients were able to discontinue regular steroids use and reported a significant improvement in their quality of life. No significant side effects were observed in any of the patients. Systemic cyclosporine is a safe and effective treatment for severe VKC. It is a steroid-sparing treatment that allows good quality of life, while keeping the disease latent.

Efficacy of Topical Niacinamide on Skin Hydration of Adolescents with Acne Vulgaris: An Experimental Study on the Adolescent Community in Jakarta, Indonesia

Background: Acne vulgaris (AV) is a chronic inflammatory skin disorder common in adolescents, often accompanied by dry, irritated skin. Topical niacinamide (vitamin B3) has shown potential in increasing skin hydration and reducing AV symptoms. This study aims to evaluate the efficacy of topical niacinamide on skin hydration in adolescents with AV in Jakarta, Indonesia. Methods: This research is a randomized controlled experimental study involving 100 adolescents (14-19 years) with mild to moderate AV in Jakarta. Participants were randomly divided into two groups: the intervention group (receiving topical 4% niacinamide cream) and the control group (receiving placebo cream). The intervention was carried out for 8 weeks, and skin hydration was measured using a corneometer at baseline, week 4, and week 8. Data analysis was carried out using paired t-tests and independent t-tests. Results: There was a significant increase in skin hydration in the intervention group compared to the control group at week 4 (p < 0.001) and week 8 (p < 0.001). No significant side effects were reported. Conclusion: Topical niacinamide was effective in increasing skin hydration in adolescents with AV in Jakarta, Indonesia. This study supports the use of topical niacinamide as an adjunct therapy in the management of AV, especially in adolescents with dry, irritated skin.

Incidence and Clinical Presentation of Severe Neurotoxicity from Nelarabine in Patients with T-Cell Acute Lymphoblastic Leukemia

BackgroundNelarabine is a purine analog with demonstrated efficacy in the treatment of T-cell Lymphoblastic Leukemia and Lymphoma (T-ALL/LBL). Despite its efficacy and excellent blood-brain barrier penetration, it has a significant side effect profile which is namely concerning for neurotoxicity. Reported neurotoxicity has varied from mild peripheral neuropathy to debilitating grade 4 neurologic complications including Guillain-Barre like syndrome and myelopathy. Patients and MethodsWe conducted a single centered, retrospective case series to study patients who developed severe neurotoxicity after receiving nelarabine as part of T-ALL treatment. One hundred thirty-five patients were identified. Thirteen patients were reviewed for severe neurotoxicity (defined as ≥grade 3), and of those five patients were deemed to have neurotoxicity secondary to nelarabine exposure. ResultsFive patients (4%) developed severe neurotoxicity as manifested by Guillain-Barre like syndrome or myelopathy within a timeframe of eight to fifty-eight days from last nelarabine dose. Upon diagnosis, patients received formal neurologic evaluation by our neuro-oncology specialists including imaging, cerebrospinal fluid testing, and electromyography. Patients were treated with IVIG, and steroids upon diagnosis, but the majority of neuro-deficits were irreversible. ConclusionOur study shows that nelarabine is generally well-tolerated, and the incidence of severe neurotoxicity is rare. Given the potential risk of severe neurotoxicity, we propose capped dose of nelarabine 1000 mg/day, neurological assessment before subsequent dosing, and avoidance of simultaneous IT therapy during nelarabine administration.

Preliminary investigation of nitric oxide release from upconverted nanoparticles excited at 808 nm near-infrared for brain tumors

Upconverted UCNPs@mSiO2-NH2 nanoparticles were synthesized via thermal decomposition while employing the energy resonance transfer principle and the excellent near-infrared (NIR) light conversion property of up-conversion. The 808 nm NIR-excited photocontrolled nitric oxide (NO) release platform was successfully developed by electrostatically loading photosensitive NO donor Roussin's black salt (RBS) onto UCNPs@mSiO2-NH2, enabling the temporal, spatial, and dosimetric regulation of NO release for biological applications of NO. The release of NO ranged from 0.015⁓0.099 mM under the conditions of 2.0 W NIR excitation power, 20 min of irradiation time, and UCNPs@mSiO2-NH2&RBS concentration of 0.25⁓1.25 mg/mL. Therefore, this NO release platform has an anti-tumor effect. In vitro experiments showed that under the NIR light, at concentrations of 0.3 mg/mL and 0.8 mg/mL of UCNPs@mSiO2-NH2&RBS, the activity of glioma (U87) and chordoma (U–CH1) cells, as measured by CCK8 assay, was reduced to 50 %. Cell flow cytometry and Western Blot experiments showed that NO released from UCNPs@mSiO2-NH2&RBS under NIR light induced apoptosis in brain tumor cells. In vivo experiments employing glioma and chordoma xenograft mouse models revealed significant inhibition of tumor growth in the NIR and UCNPs@mSiO2-NH2&RBS group, with no observed significant side effects in the mice. Therefore, NO released by UCNPs@mSiO2-NH2&RBS under NIR irradiation can be used as a highly effective and safe strategy for brain tumor therapy.

Cerebellar Non-Invasive Brain Stimulation: A Frontier in Chronic Pain Therapy.

Chronic pain poses a widespread and distressing challenge; it can be resistant to conventional therapies, often having significant side effects. Non-invasive brain stimulation (NIBS) techniques offer promising avenues for the safe and swift modulation of brain excitability. NIBS approaches for chronic pain management targeting the primary motor area have yielded variable outcomes. Recently, the cerebellum has emerged as a pivotal hub in human pain processing; however, the clinical application of cerebellar NIBS in chronic pain treatment remains limited. This review delineates the cerebellum's role in pain modulation, recent advancements in NIBS for cerebellar activity modulation, and novel biomarkers for assessing cerebellar function in humans. Despite notable progress in NIBS techniques and cerebellar activity assessment, studies targeting cerebellar NIBS for chronic pain treatment are limited in number. Nevertheless, positive outcomes in pain alleviation have been reported with cerebellar anodal transcranial direct current stimulation. Our review underscores the potential for further integration between cerebellar NIBS and non-invasive assessments of cerebellar function to advance chronic pain treatment strategies.

Intravesical Gemcitabine and Docetaxel Therapy for BCG-Naïve Patients: A Promising Approach to Non-Muscle Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) therapy for patients with non-muscle invasive bladder cancer (NMIBC) faces limitations in efficacy and significant side effects, aggravated by a recent global shortage. In this prospective clinical study, we report the outcomes of sequential intravesical administration of gemcitabine and docetaxel (Gem/Doce) as a first-line treatment for BCG-naïve patients with high-risk NMIBC (HR NMIBC). From October 2019 until April 2022, we enrolled 52 patients and followed the treatment protocol set forth by the University of Iowa. Follow-up assessments were conducted every 3 months. In this cohort, 25 (48.1%) patients were diagnosed with high-grade T1 (T1HG) bladder cancer, 10 (19.2%) patients had carcinoma in situ (CIS), and 17 (32.7%) patients had a combination of T1HG+CIS. The median time to first recurrence in the T1HG, CIS, and T1HG+CIS groups was 11, 10.5, and 8.8 months, respectively. The recurrence-free survival was 98.1%, 94.2%, and 80.8% at 6, 9, and 12 months, respectively. The rate of progression-free survival was 100%, 98.1%, and 92.3% at 6, 9, and 12 months, respectively. We demonstrated the safety and efficacy of Gem/Doce therapy in BCG-naïve patients with HR NMIBC during a one-year follow-up. Further research with extended follow-ups, as well as direct comparisons of Gem/Doce with other anticancer agents, is essential.

Lysosome-Targeted and pH-Activatable Phototheranostics for NIR-II Fluorescence Imaging-Guided Nasopharyngeal Carcinoma Phototherapy.

Currently, clinical therapeutic strategies for nasopharyngeal carcinoma (NPC) confront insurmountable dilemmas in which surgical resection is incomplete and chemotherapy/radiotherapy has significant side effects. Phototherapy offers a maneuverable, effective, and noninvasive pattern for NPC therapy. Herein, we developed a lysosome-targeted and pH-responsive nanophototheranostic for near-infrared II (NIR-II) fluorescence imaging-guided photodynamic therapy (PDT) and photothermal therapy (PTT) of NPC. A lysosome-targeted S-D-A-D-S-type NIR-II phototheranostic molecule (IRFEM) is encapsulated within the acid-sensitive amphiphilic DSPE-Hyd-PEG2k to form IRFEM@DHP nanoparticles (NPs). The prepared IRFEM@DHP exhibits a good accumulation in the acidic lysosomes for facilitating the release of IRFEM, which could disrupt lysosomal function by generating an amount of heat and ROS under laser irradiation. Moreover, the guidelines of NIR-II fluorescence enhance the accuracy of PTT/PDT for NPC and avoid damage to normal tissues. Remarkably, IRFEM@DHP enable efficient antitumor effects both in vitro and in vivo, opening up a new avenue for precise NPC theranostics.

Research Progress in Traditional Chinese Medicine Treatment of Knee Osteoarthritis

Knee osteoarthritis (KOA) is a degenerative disease characterized by pathological changes in the cartilage and subchondral bone of the knee joint. Initially, knee joint pain is the main symptom, and in the later stages, deformities and mobility disorders may occur. Modern medicine lacks effective treatment methods for early and mid stage KOA, and has drawbacks such as significant side effects and high costs. A large number of studies have confirmed that traditional Chinese medicine has unique advantages in treating KOA, and has obvious advantages such as small trauma, low cost, and definite therapeutic effect, which are gradually being accepted by a large number of KOA patients. The commonly used methods for preventing and treating KOA with traditional Chinese medicine in clinical practice include: oral administration of traditional Chinese medicine, external application of traditional Chinese medicine, fumigation, acupuncture therapy, massage therapy for regulating tendons, and targeted penetration therapy of traditional Chinese medicine. According to relevant literature, traditional Chinese medicine can significantly alleviate knee joint symptoms and improve knee joint function in patients with knee osteoarthritis, which is of great significance for the prevention and treatment of knee osteoarthritis. This article provides a review of the research progress in the prevention and treatment of KOA using traditional Chinese medicine in recent years.

Enhancing ovarian cancer treatment with maleimide-modified Pt(IV) prodrug nanoparticles

The limitations of platinum in ovarian cancer therapy, such as poor solubility and significant side effects, often lead to suboptimal therapeutic outcome and mortality. In this study, we have developed a novel approach utilizing biodegradable polymeric nanoparticles as a drug delivery system (NDDS), loaded with advanced platinum (IV) (Pt(IV)) prodrugs. A key feature of our approach is the enhancement of nanoparticles with maleimide, a modification hypothesized to significantly boost tumor tissue accumulation. When tested in mouse models of orthotopic and peritoneal metastasis ovarian cancer, these maleimide-modified nanoparticles are anticipated to show preferential accumulation in tumor tissues, enhancing therapeutic efficiency and minimizing systemic drug exposure. Our findings demonstrate that the maleimide-modified Pt(IV)-loaded NDDSs significantly reduce tumor burden in comparison to traditional cisplatin therapy, while simultaneously reducing adverse side effects. This leads to markedly improved survival rates in models of peritoneal metastasis ovarian cancer, offering a promising new direction in the treatment of this challenging disease.

A novel approach to treating post-stroke depression: administration of Botulinum Toxin A via local facial injection.

Post-stroke depression (PSD) is a frequent complication following a stroke, characterized by prolonged feelings of sadness and loss of interest, which can significantly impede stroke rehabilitation, increase disability, and raise mortality rates. Traditional antidepressants often have significant side effects and poor patient adherence, necessitating the exploration of more suitable treatments for PSD. Previous researchers and our research team have discovered that Botulinum Toxin A (BoNT-A) exhibits antidepressant effects. Therefore, our objective was to assess the efficacy and side effects of BoNT-A treatment in patients with PSD. A total of 71 stroke patients meeting the inclusion criteria were allocated to the two group. 2 cases were excluded due to severe neurological dysfunction that prevented cooperation and 4 cases were lost follow-up. Ultimately, number of participants in the BoNT-A group (n = 32) and Sertraline group (n = 33). Treatment efficacy was evaluated 1, 2, 4, 8 and 12 weeks post-treatment. There were no significant differences in baseline characteristics between the two groups (p > 0.05). Both groups exhibited comparable treatment efficacy, with fewer side effects observed in the BoNT-A group compared to the Sertraline group. BoNT-A therapy demonstrated significant effects as early as the first week (p < 0.05), and by the 12th week, there was a notable decrease in neuropsychological scores, significantly lower than the baseline level. The analysis revealed significant differences in measurements of the Hamilton Depression Scale (HAMD) (F(770) = 12.547, p = 0.000), Hamilton Anxiety Scale (HAMA) (F(951) = 10.422, p = 0.000), Self-Rating Depression Scale (SDS) (F(1385) = 10.607, p = 0.000), and Self-Rating Anxiety Scale (SAS) (F(1482) = 11.491, p = 0.000). BoNT-A treatment effectively reduces depression symptoms in patients with PSD on a continuous basis.

A comprehensive review on doxorubicin: mechanisms, toxicity, clinical trials, combination therapies and nanoformulations in breast cancer.

Doxorubicin is a key treatment for breast cancer, but its effectiveness often comes with significant side effects. Its actions include DNA intercalation, topoisomerase II inhibition, and reactive oxygen species generation, leading to DNA damage and cell death. However, it can also cause heart problems and low blood cell counts. Current trials aim to improve doxorubicin therapy by adjusting doses, using different administration methods, and combining it with targeted treatments or immunotherapy. Nanoformulations show promise in enhancing doxorubicin's effectiveness by improving drug delivery, reducing side effects, and overcoming drug resistance. This review summarizes recent progress and difficulties in using doxorubicin for breast cancer, highlighting its mechanisms, side effects, ongoing trials, and the potential impact of nanoformulations. Understanding these different aspects is crucial in optimizing doxorubicin's use and improving outcomes for breast cancer patients. This review examines the toxicity of doxorubicin, a drug used in breast cancer treatment, and discusses strategies to mitigate adverse effects, such as cardioprotective agents and liposomal formulations. It also discusses clinical trials evaluating doxorubicin-based regimens, the evolving landscape of combination therapies, and the potential of nanoformulations to optimize delivery and reduce systemic toxicity. The review also discusses the potential of liposomes, nanoparticles, and polymeric micelles to enhance drug accumulation within tumor tissues while sparing healthy organs.

Discovery of new cyclopropane sulfonamide derivatives as EGFR inhibitors to overcome C797S-mediated resistance and EGFR double mutation

The C797S mutation of EGFR leads to Osimertinib resistance by blocking the covalent binding of Cys797. To develop new agents that can overcome EGFR mutation resistance, thirty seven new cyclopropane sulfonamide derivatives were synthesized and evaluated as EGFRL858R/T790M/C797S or EGFRDel19/T790M/C797S inhibitors by structure-based screening. Most of the synthesized compounds exhibit good to excellent anti proliferation activity against to BaF3-EGFR L858R/T790M/C797S and BaF3–C797S/Del19/T790M cancer cell lines. Representative compounds 8l showed inhibitory activity against the two cancer cell lines with the IC50 values of 0.0012 and 0.0013 μM, respectively. Another compound 8h, exhibited slightly lower activity (0.0042 and 0.0034 μM of the IC50 values) to both of the two tri-mutation cell lines, but excellent activities against H1975 and PC9 cells with IC50 values of 13 and 19 nM, respectively. Considering the acquired drug resistance of tumors is a gradual process, we chose 8h for further in vivo and mechanism study. 8h was demonstrated significantly inhibited tumor growth with 72.1 % of the TGI in the BaF3/EGFR-TM xenograft tumor model and 83.5 % in the H1975-DM xenograft tumor model. Compound 8h was confirmed to be safe with no significant side effects as showed by the results of in vitro assay of human normal cells and the sections of animals major organs. Mechanism studies showed that in addition to inhibiting EGFR mutations, 8h can also target the tumor microenvironment and induce tumor cell apoptosis. All these results indicate that 8h deserves further investigation as an EGFR inhibitor to overcome C797S-mediated resistance.

Comparison of Morphine and Endomorphin Analog ZH853 for Tolerance and Immunomodulation in a Rat Model of Neuropathic Pain

µ-Opioid receptor agonists, the gold standard for analgesia, come with significant side effects when used chronically. Tolerance, defined as the decrease in analgesic activity after repeated use, remains a vital therapeutic obstacle as it increases the likelihood of dose escalation and potentially lethal side effects like respiratory depression. Previous experiments have shown that the endomorphin-1 analog, ZH853, is a specific µ-opioid receptor agonist with reduced side effects like tolerance and glial activation following chronic central administration in pain-naive animals. Here, we investigated the effects of chronic, peripheral administration of µ-opioid receptor agonists following neuropathic injury. Though µ-opioids are effective at reducing neuropathic pain, they are not recommended for first-line treatment due to negative side effects. Compared with chronic morphine, chronic ZH853 treatment led to decreased tolerance and reduced glial activation. Following twice-daily intravenous injections, morphine was less potent and had a shorter duration of antinociception compared with ZH853. Chronic morphine, but not chronic ZH853, elevated markers of activation/inflammation of astrocytes (glial fibrillary acidic protein), microglia (ionized calcium-binding adapter molecule 1), the proinflammatory cytokine tumor necrosis factor-α, and phosphorylated mitogen-activated protein (MAP) kinase p38 (pp38). By contrast, chronic ZH853 reduced ionized calcium-binding adapter molecule 1 and tumor necrosis factor-α relative to both morphine and vehicle, suggesting anti-inflammatory properties with respect to these markers. Glial fibrillary acidic protein and pp38 were not significantly different from vehicle but were significantly lower than morphine. This study demonstrates the effectiveness of chronic ZH853 for providing analgesia in a neuropathic pain state with reduced tolerance compared with morphine, potentially due to reductions in spinal glial activation. PerspectiveNeuropathic pain is generally undertreated and resistant to medication, and side-effects limit opioid treatment. Here, we show that, compared with an equiantinociceptive dose of morphine, chronic intravenous administration of endomorphin analog ZH853 led to prolonged antiallodynia, reduced tolerance, and inhibition of spinal cord neuroinflammation in male spared nerve-injured rats.

A Review of Traditional Chinese Medicine for Triple Negative Breast Cancer and the Pharmacological Mechanisms.

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Conventional treatment options for TNBC often have limited efficacy and significant side effects. In recent years, traditional Chinese medicine (TCM) has shown promising results in the treatment of TNBC. TCMs include herb combinations that have synergistic effects to regulate homeostasis in the body, reduce tumor resistance, and improve patient quality of life. At present, three main TCM methods are used to treat TNBC in the clinic: strengthening the body's resistance, dispelling phlegm, and removing cancer toxins. This paper reviews the theories and mechanisms of each in TNBC treatment. The method of strengthening the body's resistance emphasizes enhancing the body's original Qi to fight against pathogenic factors; the method of dispelling phlegm seeks to eliminate phlegm stagnation and alleviate the burden on affected organs; the method of removing cancer toxins focuses on detoxification and detumescence to remove the toxic elements associated with TNBC. Although these methods treat TNBC from different etiologies, they have achieved good therapeutic effects and represent an important academic approach: That is, to cure the disease with a comprehensive view of the body and restore the balance of Yin and Yang. This knowledge lays a foundation for the future development and reasonable application of TCM in the clinic.

Mixture of Rhodiola rosea and Nelumbo nucifera Extracts Ameliorates Sleep Quality of Adults with Sleep Disturbance.

Chronic sleep disturbance affects daily functioning, leading to decreased concentration, fatigue, and higher healthcare costs. Traditional insomnia medications are often associated with adverse side effects. This study investigated the efficacy of a novel compound derived from Rhodiola rosea and Nelumbo nucifera extracts (named RNE) in improving sleep quality with fewer side effects. The study included individuals between the ages of 20 and 65 with subthreshold insomnia and evaluated the effects of RNE on sleep, fatigue, and quality of life. Participants took 750 mg of RNE daily at bed-time for two weeks. The study used the Insomnia Severity Index (ISI), the Pittsburgh Sleep Quality Index (PSQI), a sleep diary, the Fatigue Severity Scale (FSS), and the Short Form 36 Health Survey (SF-36) for assessments. Of the 20 participants, 13 completed the study and showed significant improvements in sleep quality. The results showed improvements in ISI and PSQI scores, a 57% reduction in wake-time after sleep onset, and improved sleep efficiency. Although FSS scores remained unchanged, significant improvements were seen in SF-36 physical and mental health scores. The results suggest that RNE is an effective, low-risk option for sleep disturbance, significantly improving sleep quality and overall wellbeing without significant side effects.

Endoplasmic reticulum stress in the pathogenesis of chemotherapy-induced mucositis: Physiological mechanisms and therapeutic implications.

Chemotherapy is a common and effective treatment for cancer, but these drugs are also associated with significant side effects affecting patients' well-being. One such debilitating side effect is mucositis, characterized by inflammation, ulcerations, and altered physiological functions of the gastrointestinal (GI) tract's mucosal lining. Understanding the mechanisms of chemotherapy-induced intestinal mucositis (CIM) is crucial for developing effective preventive measures and supportive care. Chemotherapeutics not only target cancer cells but also rapidly dividing cells in the GI tract. These drugs disrupt endoplasmic reticulum (ER) homeostasis, leading to ER-stress and activation of the unfolded protein response (UPR) in various intestinal epithelial cell types. The UPR triggers signaling pathways that exacerbate tissue inflammation and damage, influence the differentiation and fate of intestinal epithelial cells, and compromise the integrity of the intestinal mucosal barrier. These factors contribute significantly to mucositis development and progression. In this review, we aim to give an in-depth overview of the role of ER-stress in mucositis and its impact on GI function. This will provide valuable insights into the underlying mechanisms and highlighting potential therapeutic interventions that could improve treatment-outcomes and the quality of life of cancer patients.

Topical treatment of pyoderma gangrenosum: A systematic review.

Systemic immunosuppressants are the mainstay of treatment for pyoderma gangrenosum (PG), but they generally have significant side effects which may be avoided by limiting treatment to topical therapy. This review aimed to assess the efficacy and safety of topical treatments for PG. An extensive literature search identified nineteen suitable publications for analysis, including two open cohort studies, five case series and twelve single case reports. The quality of evidence in the publications was graded and data relating to topical PG treatment was extracted. The lack of randomised clinical trials investigating topical monotherapy for PG means that robust statistical analysis was not possible. The greatest weight of the current evidence for topical therapy favours either corticosteroids or calcineurin inhibitors. According to our review, both these options appear well tolerated with a few side effects and may have similar efficacy in speeding up the resolution of PG ulcers. Topical therapy could be considered for use in combination with systemic treatment. There may also be a role for isolated topical monotherapy in selected patients with PG, especially those with early or mild disease and those with idiopathic PG. However further research is needed to confirm this and establish optimal treatment approaches for this condition.

Dehydroabietylamine exerts antitumor effects by affecting nucleotide metabolism in gastric cancer.

Nucleotide metabolism is the ultimate and most critical link in the self-replication process of tumors, including gastric cancer (GC). However, in clinical treatment, classic antitumor drugs such as 5-fluorouracil (5-FU) are mostly metabolic analogs of purines or pyrimidines, which lack specificity for tumor cells and therefore have significant side effects. It is unclear whether there are other drugs that can target nucleotide metabolism, except for nucleic acid analogs. Here, we found that a natural compound, dehydroabietylamine (DHAA), significantly reduced the viability and proliferation of GC cells and organoids. DHAA disrupts the purine and pyrimidine metabolism of GC cells, causing DNA damage and further inducing apoptosis. DHAA treatment decreased transcription and protein levels of key enzymes involved in the nucleotide metabolism pathway, with significant reductions in the expression of pyrimidine metabolism key enzymes CAD, DHODH, and purine metabolism key enzymes PAICS. We also found that DHAA directly binds to and reduces the expression of Forkhead box K2 (FOXK2), a common transcription factor for these metabolic enzymes. Ultimately, DHAA was shown to delay tumorigenesis in K19-Wnt1/C2mE transgenic mice model and reduce levels of CAD, DHODH, and PAICS in vivo. We demonstrate that DHAA exerts an anticancer effect on GC by targeting transcription factor FOXK2, reducing transcription of key genes for nucleotide metabolism and impairing nucleotide biosynthesis, thus DHAA is a promising candidate for GC therapy.

Benznidazole-Loaded Polymeric Nanoparticles for Oral Chemotherapeutic Treatment of Chagas Disease.

Chagas disease (CD) is a worldwide public health problem. Benznidazole (BZ) is the drug used to treat it. However, in its commercial formulation, it has significant side effects and is less effective in the chronic phase of the infection. The development of particulate systems containing BZ is therefore being promoted. The objective of this investigation was to develop polymeric nanoparticles loaded with BZ and examine their trypanocidal impact in vitro. Two formulas (BNP1 and BNP2) were produced through double emulsification and freeze drying. Subsequent to physicochemical and morphological assessment, both formulations exhibited adequate yield, average particle diameter, and zeta potential for oral administration. Cell viability was assessed in H9C2 and RAW 264.7 cells in vitro, revealing no cytotoxicity in cardiomyocytes or detrimental effects in macrophages at specific concentrations. BNP1 and BNP2 enhanced the effect of BZ within 48 h using a treatment of 3.90 μg/mL. The formulations notably improved NO reduction, particularly BNP2. The findings imply that the compositions are suitable for preclinical research, underscoring their potential as substitutes for treating CD. This study aids the quest for new BZ formulations, which are essential in light of the disregard for the treatment of CD and the unfavorable effects associated with its commercial product.

Effectiveness and patient perspective on the use of intravesical gentamicin instillations to treat recurrent urinary tract infections in neurogenic lower urinary tract dysfunction.

Patients with neurogenic lower urinary tract dysfunction (NGLUTD) who require catheterization either with clean intermittent catheters (CIC) or indwelling catheters suffer with frequent urinary tract infections (UTIs). This study assessed the efficacy, patient persistence, satisfaction, and the impact on quality of life (QoL) of gentamicin nightly bladder instillations with 15 mg. This is a prospective survey of 36 patients with NGLUTD and recurrent UTIs prescribed long-term gentamicin to prevent UTIs. Eligible patients completed a questionnaire about their use and satisfaction with gentamicin therapy, as well as survey questionnaires to address QoL. A retrospective chart review was also performed to obtain medical history, confirm drug persistence, and obtain accurate UTI data for the 12 months preceding and after starting instillations. The rate of laboratory proven symptomatic UTI requiring antibiotic treatment decreased from 3.9 to 1.1 infections per year with no increase in antibiotic resistance and no significant side effects reported by patients. Eight patients stopped therapy before a full year for various reasons, but the remaining 72% of patients have continued to use the therapy now with a mean of 4.2 years later. Satisfaction among those continuing the medication was very high. Gentamicin bladder instillations with 15 mg nightly in patients with indwelling catheters or CIC with NGLUTD are very effective and safe with high patient satisfaction. This therapy can be maintained long-term with continued efficacy.