Seed bacterization with siderophore-producing bacteria: a strategy to enhance growth and alkaloid content in Catharanthus roseus.

Catharanthus roseus is a medicinal plant widely known for producing monoterpenoid indole alkaloids (MIAs), including therapeutic compounds such as vinblastine and vincristine, which are crucial for cancer treatment. However, the naturally low concentration of these alkaloids in plant tissues poses a significant challenge for large-scale production. This study explores the application of siderophore-producing bacteria for seed bacterization of Catharanthus roseus to enhance the production of MIAs, including vindoline, catharanthine, and vinblastine.

Obesity-associated MRAP2 variants impair multiple MC4R-mediated signaling pathways.

The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor expressed at hypothalamic neurons that has an important role in appetite suppression and food intake. Mutations in MC4R are the most common cause of monogenic obesity and can affect multiple signaling pathways including Gs-cAMP, Gq, ERK1/2, β-arrestin recruitment, internalization and cell surface expression. The melanocortin-2 receptor accessory protein 2 (MRAP2), is a single-pass transmembrane protein that interacts with and regulates signaling by MC4R.

Medical students' and GP tutors' experiences of near peer teaching in primary care: a qualitative study.

Background: There exists a significant body of literature on the benefits of Peer Assisted Learning (PAL). Near-peer (NP) teaching can be defined as teaching delivered by senior students to younger year students. There are numerous examples in the literature of PAL projects in a non-clinical setting but little research in a clinical setting and even less in primary care.

Contralateral interhemispheric transcallosal transchoroidal approach to a thalamic glioma: illustrative case.

Background: Thalamic lesions located in the floor of the lateral ventricle pose significant surgical challenges, given their proximity to critical neurovascular structures. Transcortical approaches are often limited by risks of injuring the eloquent cortex and nearby vessels. Furthermore, lesions extending into the third ventricle further impede accessibility.

Surprising multifunctionality of a swim CPG neuron: C2 drives the early phase of postswim crawling despite being silent during the behavior.

In response to a suitably aversive skin stimulus, the marine mollusk launches an escape swim followed by several minutes of high-speed crawling. The two escape behaviors are highly dissimilar: whereas the swim is a muscular behavior involving alternating ventral and dorsal whole body flexions, the crawl is a nonrhythmic gliding behavior mediated by the beating of foot cilia. The serotonergic dorsal swim interneurons (DSIs) are members of the swim central pattern generator (CPG) and also strongly drive crawling.

Overcoming Drug Resistance: Novel Medications and Repositioning Strategies.

, the bacterium responsible for tuberculosis, is a global health concern, affecting millions worldwide. This bacterium has earned a reputation as a formidable adversary due to its multidrug-resistant nature, allowing it to withstand many antibiotics. The development of this drug resistance in is attributed to innate and acquired mechanisms.

Safety and Efficacy of Gamma Knife Radiosurgery for the Management of Trigeminal Neuralgia: A Retrospective and Cross-Sectional Study.

Background: Medical management is the first line of care for patients with trigeminal neuralgia (TN), and carbamazepine is the drug of choice used alone or in combination with other drugs. Gamma knife radiosurgery (GKRS) has been an established option in the management of refractory TN based on its noninvasiveness and robust safety profile. Our study aims to confirm the safety and assess the efficacy of GKRS in the management of TN.

Diagnostic performance of prospective same-day 18F-FDG PET/MRI and 18F-FDG PET/CT in the staging and response assessment of lymphoma.

Background: Accurate staging and response assessment are essential for prognosis and to guide treatment in patients with lymphoma. The aim of this study was to compare the diagnostic performance of FDG PET/MRI versus FDG PET/CT in adult patients with newly diagnosed Hodgkin and Non- Hodgkin lymphoma.

Methods: In this single centre study, 50 patients were prospectively recruited.

Ethyl Methane Sulfonate and Sodium Azide-Mediated Chemical and X-ray-Mediated Physical Mutagenesis Positively Regulate Gene Activity and Biosynthesis of Antineoplastic Vinblastine in .

synthesizes bioactive therapeutic metabolites, known as monoterpenoid indole alkaloids (MIAs), including antineoplastic vinblastine and vincristine, which have high global demand, and antihypertensive ajmalicine, a serpentine. However, the in planta biosynthesis and accumulation of these phytopharmaceuticals are very low, attributed to their high cytotoxicity in the plant. Considering the low in planta concentration and over-harvesting of plant resources, biotechnological interventions have been undertaken to enhance the production of MIAs in plant systems.

Real-World Data of a Group-Based Formula Low Energy Diet Programme in Achieving Type 2 Diabetes Remission and Weight Loss in an Ethnically Diverse Population in the UK: A Service Evaluation.

(1) Background: Formula low energy diets (LED) are effective at inducing weight loss and type 2 diabetes (T2DM) remission. However, the effect of LED programmes in ethnic minority groups in the UK is unknown. (2) Methods: A service-evaluation was undertaken of a group-based LED, total diet replacement (TDR) programme in London, UK.

Relationship between inflammatory status and microbial composition in severe asthma and during exacerbation.

Background: In T2-mediated severe asthma, biologic therapies, such as mepolizumab, are increasingly used to control disease. Current biomarkers can indicate adequate suppression of T2 inflammation, but it is unclear whether they provide information about airway microbial composition. We investigated the relationships between current T2 biomarkers and microbial profiles, characteristics associated with a Proteobacteria microbial profile and the effects of mepolizumab on airway ecology.

Astegolimab, an anti-ST2, in chronic obstructive pulmonary disease (COPD-ST2OP): a phase 2a, placebo-controlled trial.

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous inflammatory airway disease. The epithelial-derived IL-33 and its receptor ST2 have been implicated in airway inflammation and infection. We aimed to determine whether astegolimab, a selective ST2 IgG2 monoclonal antibody, reduces exacerbations in COPD.

Engineering Catharanthus roseus monoterpenoid indole alkaloid pathway in yeast.

Catharanthus roseus (Madagascar periwinkle), a medicinal plant possessing high pharmacological attributes, is widely recognized for the biosynthesis of anticancer monoterpenoid indole alkaloids (MIAs) - vinblastine and vincristine. The plant is known to biosynthesize more than 130 different bioactive MIAs, highly acclaimed in traditional and modern medicinal therapies. The MIA biosynthesis is strictly regulated at developmental and spatial-temporal stages and requires a well-defined cellular and sub-cellular compartmentation for completion of the entire MIAs biosynthesis.

Production of Effective Phyto-antimicrobials Metabolic Engineering Strategies.

The emerging outbreak of infectious diseases poses a challenge and threatens human survival. The indiscriminate use and drying pipelines of antibiotic arsenals have led to the alarming rise of drug-resistant pathogens, projecting a serious concern. The rising antimicrobial resistance and redundancy of antibiotic discovery platforms (ADPs) have highlighted the growing concern to discover new antibiotics, necessitating exploring natural products as effective alternatives to counter drug resistance.

Role of memantine in the prophylactic treatment of episodic migraine: A systematic review.

Objective: The purpose of this systematic review is to assess the efficacy and safety of memantine for the prophylactic treatment of episodic migraine.

Background: Migraine is a prevalent chronic disease with significant costs to the health care system. Although various prophylactic treatment options are available, these medications have limitations based on efficacy, potential side effects, and patient preference.

Cervicovaginal microbiota and metabolome predict preterm birth risk in an ethnically diverse cohort.

The syndrome of spontaneous preterm birth (sPTB) presents a challenge to mechanistic understanding, effective risk stratification, and clinical management. Individual associations between sPTB, self-reported ethnic ancestry, vaginal microbiota, metabolome, and innate immune response are known but not fully understood, and knowledge has yet to impact clinical practice. Here, we used multi-data type integration and composite statistical models to gain insight into sPTB risk by exploring the cervicovaginal environment of an ethnically heterogenous pregnant population (n = 346 women; n = 60 sPTB < 37 weeks' gestation, including n = 27 sPTB < 34 weeks).

Confirmation of "pre-plasmolysis mediated ex-osmosis hypothesis" to obtain shoot bud morphogenesis in Catharanthus roseus.

The antineoplastic herb, Catharanthus roseus is a classified high-value low-volume medicinal herb which is in global attention of scientific research for modulation of its monoterpenoid indole alkaloids (MIA) pathway through genetic engineering. These secondary metabolites are generally stored in specific types of structures/compartments due to their cytotoxic nature and designated roles in plant defense response. However, their presence can hinder the genetic engineering process used to develop transgenic plants through de novo morphogenesis and regeneration of plants from cultured cells/tissues and hence, it always remained a critical impediment in transgenic research in C.

An evaluation of the implementation of quality improvement (QI) in primary care dentistry: a multi-method approach.

Objectives: Ensuring that healthcare is patient-centred, safe and harm free is the cornerstone of the NHS. The Scottish Patient Safety Programme (SPSP) is a national initiative to support the provision of safe, high-quality care. SPSP promotes a coordinated approach to quality improvement (QI) in primary care by providing evidence-based methods, such as the Institute for Healthcare Improvement's Breakthrough Series Collaborative methodology.

Idiopathic gingival fibromatosis in association with aggressive periodontitis and candidal infection: A unique case report with 7-year follow-up.

Idiopathic gingival fibromatosis, also called idiopathic gingival overgrowth (IGO), is a rare benign condition that occurs either in isolation or as a part of a syndrome. The overgrowth, if excess, impedes oral functions such as mastication and speech and causes cosmetic disfigurement. Diagnosis and treatment becomes challenging if the overgrowth is massive and accompanies other associated pathologies.

Access to Shared Electronic Medical Records to Improve Adherence and Management of Discharge Medications.

The aim of the study is to assess the impact of shared electronic medical records (EMR) on the ability of pharmacists to provide medication reconciliation and clinical interventions in home-based primary care (HBPC) veterans hospitalized outside of the Veterans Affairs Medical Center (VAMC). This was a single-centered, retrospective quality improvement study. An assessment of medical records was conducted to analyze changes in ability to conduct medication reconciliations and interventions in HBPC Veterans hospitalized prior- to and postaccess to shared EMR systems with local non-VA acute care facilities.

The sputum microbiome is distinct between COPD and health, independent of smoking history.

Background: Airway bacterial dysbiosis is a feature of chronic obstructive pulmonary disease (COPD). However, there is limited comparative data of the lung microbiome between healthy smokers, non-smokers and COPD.

Methods: We compared the 16S rRNA gene-based sputum microbiome generated from pair-ended Illumina sequencing of 124 healthy subjects (28 smokers and 96 non-smokers with normal lung function), with single stable samples from 218 COPD subjects collected from three UK clinical centres as part of the COPDMAP consortium.

Detection of Cell-Dissociated Non-Typeable in the Airways of Patients with Chronic Obstructive Pulmonary Disease.

Background: Non-typeable (NTHi) is the most commonly found pathogen in the lower respiratory airways of patients with COPD. NTHi is predominantly regarded as an intracellular pathogen; however, like most pathogens, it can exist and co-exist in two broad forms: cell-associated (intracellularly or adhered to cells) or cell-dissociated (biofilm dispersed or planktonic). We sought to investigate if cell-dissociated NTHi can be detected from the sputum of COPD patients and assess this relationship to disease severity and airway inflammation.

Individual participant data (IPD)-level meta-analysis of randomised controlled trials with vitamin D-fortified foods to estimate Dietary Reference Values for vitamin D.

Context And Purpose: Individual participant data-level meta-regression (IPD) analysis is superior to meta-regression based on aggregate data in determining Dietary Reference Values (DRV) for vitamin D. Using data from randomized controlled trials (RCTs) with vitamin D-fortified foods, we undertook an IPD analysis of the response of winter serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among children and adults and derived DRV for vitamin D.

Methods: IPD analysis using data from 1429 participants (ages 2-89 years) in 11 RCTs with vitamin D-fortified foods identified via a systematic review and predefined eligibility criteria.