Reversal agents

IMPORTANCE: In newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), disease progression due to acquired resistance to first- or second-generation BCR::ABL1 tyrosine kinase inhibitors is common. Ponatinib inhibits BCR::ABL1 and all single-mutation variants, including T315I. OBJECTIVE: To compare frontline ponatinib vs imatinib in adults with newly diagnosed Ph+ ALL. DESIGN, SETTING, AND PARTICIPANTS: Global registrational, phase 3, open-label trial in adults aged 18 years or older with newly diagnosed Ph+ ALL...

After chemotherapy, tumor cells tend to become more aggressive, making it challenging for natural and adaptive immune responses to fight them. This often results in recurrence and metastasis, leading to higher mortality rates. The purpose of this study is to discover the mechanisms that cause chemotherapy resistance, including altered expression of immune checkpoints, in a colorectal cancer cell line. We used conventional methods to culture the SW-1116 colorectal cancer cell line in this study. The MTT assay was used to determine the IC50 and efficacy of Docetaxel and Doxorubicin...

INTRODUCTION: Despite the well-recognized health benefits, the mechanisms and site of action of metformin remains elusive. Metformin-induced global lipidomic changes in plasma of animal models and human subjects have been reported. However, there is a lack of systemic evaluation of metformin-induced lipidomic changes in different tissues. Metformin uptake requires active transporters such as organic cation transporters (OCTs), and hence, it is anticipated that metformin actions are tissue-dependent...

In addressing the increasing demand for wearable sensing systems, the performance and lifespan of such devices must be improved by enhancing their sensitivity and healing capabilities. The present work introduces an innovative method for synthesizing a healable disulfide bond contained in a polydimethylsiloxane network (PDMS-SS) that incorporates ionic salts, which is designed to serve as a highly effective dielectric layer for capacitive tactile sensors. Within the polymer network structure, the cross-linking agent pentaerythritol tetrakis 3-mercaptopropionate (PTKPM) forms reversible disulfide bonds while simultaneously increasing polymer softness and the dielectric constant...

Candida glabrata is an important opportunistic human pathogen well known to develop resistance to antifungal drugs. Due to their numerous desirable qualities, antimicrobial lipopeptides have gained significant attention as promising candidates for antifungal drugs. In the present study, two bioactive lipopeptides (AF4 and AF5 m/z 1071.5 and 1085.5, respectively), coproduced and purified from Bacillus subtilis RLID12.1, consist of seven amino acid residues with lipid moieties . In our previous studies, the reversed phased-HPLC purified lipopeptides demonstrated broad-spectrum of antifungal activities against over 110 Candida albicans, Candida non -albicans and mycelial fungi...

Injectable anticoagulants are widely used in medical procedures to prevent unwanted blood clotting. However, many lack safe, effective reversal agents. Here, we present new data on a previously described RNA origami-based, direct thrombin inhibitor (HEX01). We describe a new, fast-acting, specific, single-molecule reversal agent (antidote) and present in vivo data for the first time, including efficacy, reversibility, preliminary safety, and initial biodistribution studies. HEX01 contains multiple thrombin-binding aptamers appended on an RNA origami...

To investigate the role of microRNA-195-3p (miR-195-3p) in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury. AC16 human cardiomyocyte cells were cultured and pretreated with different concentrations of isoflurane (ISO) (1%, 2%, and 3%), followed by 6 h each of hypoxia and reoxygenation to construct H/R cell models. The optimum ISO concentration was assessed based on the cell viability. miR-195-3p expression was regulated by in vitro cell transfection. Cell viability was determined by MTT assay, and apoptosis was evaluated by flow cytometry...

DNA topoisomerase IIα (TOP2α, 170kDa, TOP2α/170) is an essential enzyme for proper chromosome dysjunction by producing transient DNA double-stranded breaks and is a significant target for DNA damage stabilizing anti-cancer agents such as etoposide. Therapeutic effects of TOP2α poisons can be limited due to acquired drug resistance. We previously demonstrated decreased TOP2α/170 levels in an etoposide-resistant human leukemia K562 subline, designated K/VP.5, accompanied by increased expression of a C-terminal truncated TOP2α isoform (90 kDa, TOP2α/90) which heterodimerized with TOP2α/170 and was a determinant of resistance by exhibiting dominant-negative effects against etoposide activity...

Osteoarthritis (OA) is a chronic degenerative disease with a significant prevalence that causes cartilage damage and can lead to disability. The main factors contributing to the onset and progression of OA include inflammation and degeneration of the extracellular matrix. Cathelicidin-BF (BF-30), a natural peptide derived from Bungarus fasciatus venom, has shown multiple important pharmacological effects. However, the action mechanism of BF-30 in OA treatment remains to be elucidated. In this research, X-ray and Safranin O staining were employed to evaluate the imageology and histomorphology differences in the knee joints of mice in vivo...

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has a poor prognosis despite advances in multidisciplinary treatments and immune checkpoint inhibitors. We previously reported that neural pentraxin receptor (NPTXR), a transmembrane protein mainly expressed in the brain and involved in synaptic transmission, is implicated in gastric cancer malignancy. This study evaluated the expression and function of NPTXR in ESCC, the therapeutic potential of monoclonal antibody (mAb) against NPTXR, and its prognostic value in ESCC patients...

The present study evaluated a range of biological activities of Euphorbia tithymaloides L. (Family: Euphorbiaceae) in relation to diabetes and associated complications. This plant has antioxidant and anti-inflammatory properties, but its potential for the management of hyperglycaemia and subsequently, the inhibition and reversal of advanced glycation end products has not yet been pinpointed. The objectives of this work centred around comparative iv-vitro phytochemical screening of different plant parts, followed by antidiabetic, antiglycation and glycation-reversing activities of Euphorbia tithymaloides ...

Patients undergoing chemotherapy with cisplatin commonly present gastrointestinal effects such as constipation and gastric emptying (GE) delay. Both the purinergic system and physical exercise modulate the gastrointestinal (GI) tract. In the current study, we investigated the role of ATP, physical exercise, and P2X7 receptor blocking on GE delay induced by cisplatin in rats. Male rats were divided into the following groups: control (C), cisplatin (Cis), exercise (Ex), Brilliant Blue G (BBG), ATP, Cis+Ex, Cis+ATP, Cis+BBG, Cis+Ex+BBG, Cis+Ex+BBG+ATP, and Cis+ATP+BBG...

Valproic acid holds a prominent position as the primary therapeutic option for epilepsy cases. The utilization of antiepileptic agents like valproic acid has been linked to disturbances in sleep architecture. Although scant, there exists a subset of studies that allude to the potential manifestation of sleep apnea as an adverse effect of valproic acid administration. In this context, we present a case report of a 76-year-old man with a past medical history of arterial hypertension, atrial fibrillation, and obstructive sleep apnea syndrome treated with continuous positive airway pressure since 2020...

BACKGROUND Rapid diagnosis is critical for effective treatment of severe pneumonia during the COVID-19 pandemic. Chlamydia psittaci, an atypical community-acquired pathogen, typically exhibits nonspecific clinical signs and requires stringent conditions for microbiological culture, complicating its identification. Metagenomic next-generation sequencing (mNGS), which involves shotgun sequencing of DNA or RNA from clinical samples, is a key technology in clinical settings. Although mNGS technology identifies nucleic acids, it should not be directly equated with the presence of pathogenic microorganisms...

AIMS: γ-aminobutyric acid (GABA) from reactive astrocytes is critical for the dysregulation of neuronal activity in various neuroinflammatory conditions. While Scutellaria baicalensis Georgi (S. baicalensis) is known for its efficacy in addressing neurological symptoms, its potential to reduce GABA synthesis in reactive astrocytes and the associated neuronal suppression remains unclear. This study focuses on the inhibitory action of monoamine oxidase B (MAO-B), the key enzyme for astrocytic GABA synthesis...

BACKGROUND: Adenosine A3 receptor (ADORA3) belongs to the adenosine receptor families and the role of ADORA3 in vascular dementia (VaD) is largely unexplored. The present study sought to determine the therapeutic role of ADORA3 antagonist in a mouse model of VaD. METHODS: The GSE122063 dataset was selected to screen the differential expression genes and pathways between VaD patients and controls. A mouse model of bilateral carotid artery stenosis (BCAS) was established...

Spartina alterniflora Loisel, a perennial grass, has become an invasive species in China's coastal wetlands (Zhang et al. 2018). In July 2021, brown spot symptoms were observed on S. alterniflora in a coastal wetland (21°45'48″N, 108°44'00″E) in Beihai City, Guangxi Province, China. The disease affected approximately 50% of the plants in the surveyed area (0.2 ha) and was also observed in other regions of Beihai. It caused brown lesions with a gray or whitish center on the leaves and stems of S...

Reverse zoonotic respiratory diseases threaten great apes across Sub-Saharan Africa. Studies of wild chimpanzees have identified the causative agents of most respiratory disease outbreaks as "common cold" paediatric human pathogens, but reverse zoonotic transmission pathways have remained unclear. Between May 2019 and August 2021, we conducted a prospective cohort study of 234 children aged 3-11 years in communities bordering Kibale National Park, Uganda, and 30 adults who were forest workers and regularly entered the park...

Launaea fragilis (Asso) Pau is a Cholistan desert medicinal plant. Launaea species are used as traditional remedies against various inflammatory conditions. The current research was designed to evaluate the anti-nociceptive, anti-inflammatory, and anti-arthritic potential of ethanolic extract of L. fragilis (Et-LF). The plant extract was prepared by triple maceration. GC-MS screening explored the presence of various bioactive phytoconstituents including n-tetracosanol-1, 1-heptacosanol, and n-hexadecanoic acid...

Oncogene activation and epigenome dysregulation drive tumor initiation and progression, contributing to tumor immune evasion and compromising the clinical response to immunotherapy. Epigenetic immunotherapy represents a promising paradigm in conquering cancer immunosuppression, whereas few relevant drug combination and delivery strategies emerge in the clinic. This study presents a well-designed triune nanomodulator, termed ROCA, which demonstrates robust capabilities in tumor epigenetic modulation and immune microenvironment reprogramming for cancer epigenetic immunotherapy...