ABSTRACT
Gastrointestinal malignancies are one of the major worldwide health concerns. In the present review, we have assessed the plausible therapeutic implication of Ursolic Acid (UA) against gastrointestinal cancer. By modulating several signaling pathways critical in cancer development, UA could offer anti-inflammatory, anti-proliferative, and anti-metastatic properties. However, being of low oral bioavailability and poor permeability, its clinical value is restricted. To deliver and protect the drug, liposomes and polymer micelles are two UA nanoformulations that can effectively increase medicine stability. The use of UA for treating cancers is safe and appropriate with low toxicity characteristics and a predictable pharmacokinetic profile. Although the bioavailability of UA is limited, its nanoformulations could emerge as an alternative to enhance its efficacy in treating GI cancers. Further optimization and validation in the clinical trials are necessary. The combination of molecular profiling with nanoparticle-based drug delivery technologies holds the potential for bringing UA to maximum efficacy, looking for good prospects with GI cancer treatment.
ABSTRACT
Due to the increasing incidence of cancer and the difficulties in determining the safety profile of existing therapeutic approaches, cancer research has recently become heavily involved in the search for new therapeutic approaches. The therapeutic significance of natural substances, especially flavonoids, against the onset and progression of cancer has been emphasized in traditional food-based medicine. Interestingly, the flavone luteolin possesses biological effects that have been linked to its anti-inflammatory, antioxidant, and anticancer effects. Luteolin interacts with several downstream chemicals and signaling pathways, including those involved in apoptosis, autophagy, cell cycle progression, and angiogenesis, to exert its anticancer effects on various cancerous cells. A complete understanding of both intrinsic and extrinsic apoptotic pathways, autophagy, and, most critically, the nanodelivery of luteolin in liver cancer is provided in the current review.
Subject(s)
Apoptosis , Liver Neoplasms , Luteolin , Signal Transduction , Luteolin/pharmacology , Luteolin/therapeutic use , Humans , Apoptosis/drug effects , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Signal Transduction/drug effects , Autophagy/drug effects , Animals , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacologyABSTRACT
Platelet CLEC-2 is a hemITAM-containing receptor which has a critical role in venous thrombosis, but minimal involvement in haemostasis. CLEC-2 can be blocked by Btk inhibitors. Treatment with ibrutinib is associated with increased bleeding due to off-target inhibition of Src family kinases (SFKs). Patients with X-linked agammaglobulinemia (XLA) who lack Btk however do not bleed, suggesting selective Btk inhibition is a viable antithrombotic strategy. We assessed the effects of selective Btk inhibitors PRN1008 (rilzabrutinib) and PRN473 on platelet signalling and function mediated by CLEC-2 and GPVI. We used healthy donor and XLA platelets to determine off-target inhibitor effects. Inferior vena cava (IVC) stenosis and Salmonella infection mouse models were used to assess antithrombotic effects of PRN473 in vivo. PRN1008 and PRN473 potently inhibited CLEC-2-mediated platelet activation to rhodocytin. No off-target inhibition of SFKs was seen. PRN1008 treatment of Btk-deficient platelets resulted in minor additional inhibition of aggregation and tyrosine phosphorylation, likely reflecting inhibition of Tec. No effect on GPCR-mediated platelet function was observed. PRN473 significantly reduced the number of thrombi in podoplanin positive vessels following Salmonella infection and the presence of IVC thrombosis following vein stenosis. The potent inhibition of human platelet CLEC-2, and reduced thrombosis in in vivo models, together with the lack of off-target SFK inhibition and absence of bleeding reported in rilzabrutinib treated immune thrombocytopenia patients, suggest Btk inhibition as a promising antithrombotic strategy.
ABSTRACT
Gastrointestinal cancers continue to pose a significant global health challenge, with millions of new cases diagnosed each year. Despite advancements in treatment, the prognosis for many patients remains poor. This article explores the potential of garcinol, a polyisoprenylated benzophenone found in various Garcinia species, as a therapeutic agent against gastrointestinal malignancies. The objective is to review recent research on garcinol's anticancer properties, its mechanisms of action, and safety aspects. Garcinol exhibits anticancer effects in esophageal, gastric, colorectal, pancreatic, and liver cancers by inhibiting metastasis, inducing apoptosis, and targeting key molecular pathways in cancer progression. Nanotechnology is explored as a means to enhance garcinol delivery and efficacy. Safety assessments suggest a promising toxicity profile. Garcinol shows significant potential as a natural therapeutic agent for gastrointestinal cancers, and future research is needed on optimizing its delivery, exploring synergistic combinations, and conducting clinical trials to validate its efficacy and safety for clinical applications.
Subject(s)
Gastrointestinal Neoplasms , Terpenes , Humans , Gastrointestinal Neoplasms/prevention & control , Gastrointestinal Neoplasms/drug therapy , Terpenes/therapeutic use , Terpenes/pharmacology , Animals , Antineoplastic Agents, Phytogenic/therapeutic use , Antineoplastic Agents, Phytogenic/pharmacologyABSTRACT
Currently, climate change-related environmental issues associated with agriculture is alarming and poses a potential risk to global food security, causing significant global concern as a result [...].
ABSTRACT
Polypharmacy in psychiatry is an in-depth examination of drug-drug interactions and treatment challenges that explores the intricate landscape of psychiatric polypharmacy, a practice involving the prescription of multiple medications to individuals with mental health disorders. This review is based on the critical aspects of drug-drug interactions and the associated treatment challenges. Psychiatric polypharmacy is motivated by the complexity of mental health conditions, where monotherapy may be insufficient. While it offers potential benefits, the practice raises concerns related to drug interactions that can compromise safety and efficacy. The review delves into the prevalence and clinical indications for psychiatric polypharmacy, thoroughly analyzing drug interactions, treatment challenges, and strategies for mitigation. Real-world case studies illustrate the complexities and outcomes of managing complex medication regimens, while emerging trends in personalized medicine, advancements in psychopharmacology, multidisciplinary approaches, and digital health solutions offer a glimpse into the future of psychiatric polypharmacy. This examination underscores the importance of a patient-centered, evidence-based approach in optimizing psychiatric polypharmacy to achieve therapeutic benefits while minimizing risks.
Subject(s)
Drug Interactions , Mental Disorders , Polypharmacy , Humans , Mental Disorders/drug therapy , Psychotropic Drugs/therapeutic use , PsychiatryABSTRACT
Overuse of antibiotics is accelerating the antimicrobial resistance among pathogenic microbes which is a growing public health challenge at the global level. Higher resistance causes severe infections, high complications, longer stays at hospitals and even increased mortality rates. Antimicrobial resistance (AMR) has a significant impact on national economies and their health systems, as it affects the productivity of patients or caregivers due to prolonged hospital stays with high economic costs. The main factor of AMR includes improper and excessive use of antimicrobials; lack of access to clean water, sanitation, and hygiene for humans and animals; poor infection prevention and control measures in hospitals; poor access to medicines and vaccines; lack of awareness and knowledge; and irregularities with legislation. AMR represents a global public health problem, for which epidemiological surveillance systems have been established, aiming to promote collaborations directed at the well-being of human and animal health and the balance of the ecosystem. MDR bacteria such as E. coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus spp., Acinetobacter spp., and Klebsiella pneumonia can even cause death. These microorganisms use a variety of antibiotic resistance mechanisms, such as the development of drug-deactivating targets, alterations in antibiotic targets, or a decrease in intracellular antibiotic concentration, to render themselves resistant to numerous antibiotics. In context, the United Nations issued the Sustainable Development Goals (SDGs) in 2015 to serve as a worldwide blueprint for a better, more equal, and more sustainable existence on our planet. The SDGs place antimicrobial resistance (AMR) in the context of global public health and socioeconomic issues; also, the continued growth of AMR may hinder the achievement of numerous SDGs. In this review, we discuss the role of environmental pollution in the rise of AMR, different mechanisms underlying the antibiotic resistance, the threats posed by pathogenic microbes, novel antibiotics, strategies such as One Health to combat AMR, and the impact of resistance on sustainability and sustainable development goals.
ABSTRACT
Self-nano Emulsifying Drug Delivery Systems (SNEDDS) are novel formulations that can enhance the solubility and bioavailability of poorly water-soluble drugs. SNEDDS are composed of lipids, surfactants, co-solvents, and drugs and can spontaneously form nanoemulsions when mixed with water under mild agitation. SNEDDS can be formulated as liquid or solid dosage forms and can improve drug absorption by increasing the interfacial area, protecting the drug from degradation, and facilitating lymphatic transport. SNEDDS is characterized by various parameters such as particle size, zeta potential, droplet morphology, emulsification efficiency, drug solubility, and stability. SNEDDS offers several advantages over conventional dosage forms, such as dose reduction, faster onset of action, reduced variability, versatility, and ease of formulation. However, SNEDDS also face some limitations and challenges, such as drug precipitation, cost-effectiveness, compatibility with capsule shells, and lack of predictive in vitro models. SNEDDS has a promising future in the field of pharmaceuticals, especially for personalized medicine and targeted drug delivery.
Subject(s)
Drug Delivery Systems , Emulsions , Solubility , Water , Emulsions/chemistry , Humans , Pharmaceutical Preparations/administration & dosage , Pharmaceutical Preparations/chemistry , Water/chemistry , Nanoparticles/chemistry , Drug DevelopmentABSTRACT
Background and Purpose: Empathy is essential in patient-centered compassionate health care. Lack of formal training, workload, patient factors, and digitalization have been attributed to its regression. Empathy can be nurtured by educational interventions. A structured empathy education module for postgraduate trainees is not available in India. The aim for this research was to develop, deliver, and evaluate one for ophthalmology postgraduate trainees. Methodology: This interventional study was conducted in the tertiary ophthalmology department of Western India during 2022-2023. Four workshops comprising of interactive lectures, literature, creative arts, and role plays were delivered with trained facilitators. Data from surveys for trainee self-assessment, patient perception of trainee empathy, pre-post knowledge test, and trainee and facilitator feedback were collected and analyzed. Results: Seventy-nine ophthalmology postgraduate trainees participated in this intervention. Excessive workload and lack of training were shared as the barriers to empathetic care. Trainees showed improved knowledge, skills, and attitude in empathy after the workshops. The facilitators and trainees were satisfied with the learning goals, execution, utility, feasibility, and relevance of the workshops. Ninety-three percent trainees want this module to be a part of postgraduate curriculum. Conclusion: This study substantiates the use of structured interactive training for cultivating empathy in postgraduate trainees. Barriers against empathy were identified and can be mitigated by restorative measures. Literature, arts, and role plays are the effective education tools for empathy.
ABSTRACT
Bioremediation of surfactants in water bodies holds significant ecological importance as they are contaminants of emerging concern posing substantial threats to the aquatic environment. Microbes exhibiting special ability in terms of bioremediation of contaminants have always been reported to thrive in extraordinary environmental conditions that can be extreme in terms of temperature, lack of nutrients, and salinity. Therefore, in the present investigation, a total of 46 bacterial isolates were isolated from the Indian sector of the Southern Ocean and screened for degradation of sodium dodecyl sulphate (SDS). Further, two Gram-positive psychrotolerant bacterial strains, ASOI-01 and ASOI-02 were identified with significant SDS degradation potential. These isolates were further studied for growth optimization under different environmental conditions. The strains were characterized as Staphylococcus saprophyticus and Bacillus pumilus based on morphological, biochemical, and molecular (16S RNA gene) characteristics. The study reports 88.9% and 93.4% degradation of SDS at a concentration of 100 mgL-1, at 20 °C, and pH 7 by S. saprophyticus ASOI-01 and B. pumilus ASOI-02, respectively. The experiments were also conducted in wastewater samples where a slight reduction in degradation efficiency was observed with strains ASOI-01 and ASOI-02 exhibiting 76.83 and 64.93% degradation of SDS respectively. This study infers that these bacteria can be used for the bioremediation of anionic surfactants from water bodies and establishes the potential of extremophilic microbes for the utilization of sustainable wastewater management.
Subject(s)
Bacillus pumilus , Biodegradation, Environmental , Seawater , Sodium Dodecyl Sulfate , Staphylococcus saprophyticus , Sodium Dodecyl Sulfate/metabolism , Bacillus pumilus/genetics , Bacillus pumilus/metabolism , Bacillus pumilus/isolation & purification , Bacillus pumilus/classification , Staphylococcus saprophyticus/genetics , Staphylococcus saprophyticus/isolation & purification , Staphylococcus saprophyticus/metabolism , Staphylococcus saprophyticus/classification , Seawater/microbiology , Surface-Active Agents/metabolism , Phylogeny , RNA, Ribosomal, 16S/genetics , Water Pollutants, Chemical/metabolism , Wastewater/microbiologyABSTRACT
Recent years have witnessed the rise of more recent pandemic outbreaks including COVID-19 and monkeypox. A multinational monkeypox outbreak creates a complex situation that necessitates countermeasures to the existing quo. The first incidence of monkeypox was documented in the 1970s, and further outbreaks led to a public health emergency of international concern. Yet as of right now, neither vaccines nor medicines are certain to treat monkeypox. Even the inability of conducting human clinical trials has prevented thousands of patients from receiving effective disease management. The current state of the disease's understanding, the treatment options available, financial resources, and lastly international policies to control an epidemic state are the major obstacles to controlling epidemics. The current review focuses on the epidemiology of monkeypox, scientific ideas, and available treatments, including potential monkeypox therapeutic methods. As a result, a thorough understanding of monkeypox literature will facilitate in the development of new therapeutic medications for the prevention and treatment of monkeypox.
Subject(s)
Cytosine/analogs & derivatives , Mpox (monkeypox) , Organophosphonates , Humans , Cidofovir , BenzamidesABSTRACT
[This corrects the article DOI: 10.3389/fbioe.2022.1025405.].
ABSTRACT
Flavopiridol is a flavone synthesized from the natural product rohitukine, which is derived from an Indian medicinal plant, namely Dysoxylum binectariferum Hiern. A deeper understanding of the biological mechanisms by which such molecules act may allow scientists to develop effective therapeutic strategies against a variety of life-threatening diseases, such as cancer, viruses, fungal infections, parasites, and neurodegenerative diseases. Mechanistic insight of flavopiridol reveals its potential for kinase inhibitory activity of CDKs (cyclin-dependent kinases) and other kinases, leading to the inhibition of various processes, including cell cycle progression, apoptosis, tumor proliferation, angiogenesis, tumor metastasis, and the inflammation process. The synthetic derivatives of flavopiridol have overcome a few demerits of its parent compound. Moreover, these derivatives have much improved CDK-inhibitory activity and therapeutic abilities for treating severe human diseases. It appears that flavopiridol has potential as a candidate for the formulation of an integrated strategy to combat and alleviate human diseases. This review article aims to unravel the potential therapeutic effectiveness of flavopiridol and its possible mechanism of action.
Subject(s)
Antineoplastic Agents , Neoplasms , Humans , Flavonoids/pharmacology , Flavonoids/therapeutic use , Cyclin-Dependent Kinases , Phosphorylation , Neoplasms/drug therapy , Antineoplastic Agents/pharmacology , ApoptosisABSTRACT
Small cell neuroendocrine carcinoma of nasopharynx is extremely rare and displays aggressive nature with a poor prognosis. Neuroendocrine tumours rarely arise from the head and neck region and pose a diagnostic and management challenge. In English literature, only 16 cases of primary small cell neuroendocrine carcinoma of nasopharynx have been reported so far; and to the best of our knowledge, this is the seventeenth case and second in the younger age group. Here, we report the case of an adolescent male patient who presented with nasal blockage, repeated episodes of epistaxis and neck swellings. After proper diagnostic workup, the diagnosis of small cell neuroendocrine carcinoma of nasopharynx was made. The patient was treated with chemotherapy, followed by radiotherapy. Imaging investigation executed after the end of the treatment exhibited complete remission of the disease. The patient is kept under active surveillance with no signs of relapse at present.
ABSTRACT
As a result of the increasing incidence of cirrhosis in the UK, more patients with chronic liver disease are being considered for elective non-hepatic surgery. A historical reluctance to offer surgery to such patients stems from general perceptions of poor postoperative outcomes. While this is true for those with decompensated cirrhosis, selected patients with compensated early-stage cirrhosis can have good outcomes after careful risk assessment. Well-recognised risks include those of general anaesthesia, bleeding, infections, impaired wound healing, acute kidney injury and cardiovascular compromise. Intra-abdominal or cardiothoracic surgery are particularly high-risk interventions. Clinical assessment supplemented by blood tests, imaging, liver stiffness measurement, endoscopy and assessment of portal pressure (derived from the hepatic venous pressure gradient) can facilitate risk stratification. Traditional prognostic scoring systems including the Child-Turcotte-Pugh and Model for End-stage Liver Disease are helpful but may overestimate surgical risk. Specific prognostic scores like Mayo Risk Score, VOCAL-Penn and ADOPT-LC can add precision to risk assessment. Measures to mitigate risk include careful management of varices, nutritional optimisation and where possible addressing any ongoing aetiological drivers such as alcohol consumption. The role of portal decompression such as transjugular intrahepatic portosystemic shunting can be considered in selected high-risk patients, but further prospective study of this approach is required. It is of paramount importance that patients are discussed in a multidisciplinary forum, and that patients are carefully counselled about potential risks and benefits.
ABSTRACT
The Yamuna River, a tributary of the holy Ganga, is heavily polluted in the Delhi-NCR region, India and has been gaining attention due to the excessive foaming of the river over the past few years. This can be directly or indirectly related to the overuse of surfactants and the discharge of untreated domestic and textile wastewater into the river. To determine the surfactant load and investigate potential surfactant-degrading bacteria in the region, 96 water samples from four sites in the Okhla Barrage stretch of the river were collected and analysed. The results showed that the selected sites have surfactant concentrations more than the permissible limit (1.00 mgL-1). Also, at most of the sites, the concentration crossed the desirable limit of BIS (0.2 mgL-1) during the period of analysis. The concentration of anionic surfactant reported in the region was found in the range of 0.29 mgL-1 and 2.83 mgL-1. A total of 38 different bacteria were isolated using selective media from the same water samples, out of which 7 bacterial isolates were screened for sodium dodecyl sulphate (SDS) tolerance activity. Based on 16S rRNA gene sequencing, 2 species, namely Pseudomonas koreensis YRW-02 and Pseudomonas songnenensis YRW-05 have been identified and their degradation potential was assessed at different SDS concentrations. The results showed that our strains YRW-02 and YRW-05 degraded 78.29 and 69.24% of SDS respectively. Growth optimization was also performed at different substrate concentrations, pH, and temperature to investigate optimum degradation conditions. This study plays a significant role in assessing the surfactant load and also gives a promising background for future use in in-situ bioremediation experiments.
ABSTRACT
[This corrects the article DOI: 10.1007/s12298-023-01315-7.].