Treatment Of Several Diseases Research Articles

Natural products and diet for the prevention of oral cancer: Research from south and southeast Asia.

Medicinal plants are of prime importance in the discovery of drugs. They are an inherent source of naturally available phytochemicals that can help in the prevention and treatment of several diseases including cancer. This article reviews the experimental and clinical evidence of phytochemicals available in natural dietary products that are used in everyday life across South Asia and South-East Asia for their perceived effectiveness in the management of Potentially Malignant Disorders and prevention of Oral Cancer. The review also highlights the active phytometabolites, their invitro anti-proliferative properties and targeted signalling pathways, biological activities in invivo models and translative potential for clinical trials in humans.

Ethnomedicine, antibacterial activity, antioxidant potential and phytochemical screening of selected medicinal plants in Dibatie district, Metekel zone, western Ethiopia.

Medicinal plants play a major role in the delivery of healthcare, particularly among the rural population of Ethiopia. Plant extracts and their bioactive compounds have been utilized for the treatment of several diseases. This study was aimed at evaluating the antibacterial activity, antioxidant capacity, and phytochemical content of selected medicinal plants used in Dibatie district, western Ethiopia. Study plants were collected, shade dried, pulverized, extracted by maceration in 80% ethanol, and subjected to antibacterial, antioxidant, and phytochemical tests. Minimum inhibitory concentration (MIC) was determined using 96-well microplates and nutrient broth microdilution. Antioxidant activity was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. Phytochemical screening was conducted using standard test methods. The ethanolic extract of Polystachya steudneri Rchb.f. pseudobulbs was the most active against gram-negative Proteus mirabilis, Salmonella typhimurium, Klebsiella pneumoniae, Escherichia coli, and Shigella flexneri, with MIC values of 8 ± 0, 11 ± 5, 3 ± 1, 3 ± 1, and 2 ± 0mg/mL, respectively. The ethanolic extract of P. steudneri was also the most effective against gram-positive Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus agalactiae, and Enterococcus faecalis, with MIC values of 8 ± 0, 8 ± 0, 3 ± 1, and 16 ± 0mg/mL, respectively. Ethanolic extracts of Gnidia involucrata Steud. ex A.Rich. stems and roots were effective antioxidants, with respective 50% DPPH free radical inhibitory concentrations (IC50) of 168.68 and 181.79µg/mL, followed by that of P. steudneri (IC50 = 203.11µg/mL). The study plants contained alkaloids, anthocyanins, anthraquinones, cardiac glycosides, coumarins, flavonoids, phenols, saponins, steroids, tannins, and terpenoids. This study confirmed the antibiotic, antioxidant, and phytochemical constituents of the investigated plants and suggested further investigations that may lead to bioactive lead compounds.

Comparison of the Differences between Two-Photon Excitation, Upconversion, and Conventional Photodynamic Therapy on Cancers in In Vitro and In Vivo Studies

Photodynamic therapy (PDT) is a minimally invasive treatment for several diseases. It combines light energy with a photosensitizer (PS) to destroy the targeted cells or tissues. A PS itself is a non-toxic substance, but it becomes toxic to the target cells through the activation of light at a specific wavelength. There are some limitations of PDT, although it has been used in clinical studies for a long time. Two-photon excitation (TPE) and upconversion (UC) for PDT have been recently developed. A TPE nanoparticle-based PS combines the advantages of TPE and nanotechnology that has emerged as an attractive therapeutic agent for near-infrared red (NIR) light-excited PDT, whilst UC is also used for the NIR light-triggered drug release, activation of ‘caged’ imaging, or therapeutic molecules during PDT process for the diagnosis, imaging, and treatment of cancers. Methods: Nine electronic databases were searched, including WanFang Data, PubMed, Science Direct, Scopus, Web of Science, Springer Link, SciFinder, and China National Knowledge Infrastructure (CNKI), without any language constraints. TPE and UCNP were evaluated to determine if they had different effects from PDT on cancers. All eligible studies were analyzed and summarized in this review. Results: TPE-PDT and UCNP-PDT have a high cell or tissue penetration ability through the excitation of NIR light to activate PS molecules. This is much better than the conventional PDT induced by visible or ultraviolet (UV) light. These studies showed a greater PDT efficacy, which was determined by enhanced generation of reactive oxygen species (ROS) and reduced cell viability, as well as inhibited abnormal cell growth for the treatment of cancers. Conclusions: Conventional PDT involves Type I and Type II reactions for the generation of ROS in the treatment of cancer cells, but there are some limitations. Recently, TPE-PDT and UCNP-PDT have been developed to overcome these problems with the help of nanotechnology in in vitro and in vivo studies.

Evaluation of the antioxidant and anti-inflammatory properties of the hydroethanolic extract of the leaves of <i>Blighia sapida</i> KD Koenig

Blighia sapida is widely used in traditional medicine for the treatment of several diseases in Togo. This study aimed to assess the antioxidant and anti-inflammatory properties of Blighia sapida. To this end, a phytochemical screening was carried out, followed by an assessment of DPPH, total antioxidant capacity, ex vivo lipoperoxidation tests on Sprague Dawley rats, and an evaluation of anti- inflammatory activity by the egg albumin denaturation test. The leaves extract scavenged the DPPH free radical with an IC50 of 172 ± 0.577µg/mL and its total antioxidant capacity value was 40.174 ± 0.638 mg Eq AA/g. In the ex vivo lipoperoxidation test on the kidney and liver, the extract showed a significant inhibitory effect. Phytochemical tests revealed the presence of tannins, flavonoids, alkaloids, saponosides, and carbohydrate compounds. The present results showed that Blighia sapida leaves possess antioxidant and anti- inflammatory properties which may be linked to the bioactive compounds they contain, suggesting their use to prevent oxidative and inflammatory processes.

Terpenes as Potential Anti-Alzheimer’s Disease Agents

Alzheimer’s disease (AD), a slowly progressive neurodegenerative disorder, is the main cause of dementia worldwide. However, currently, the approved drugs to combat AD are effective only in treating its symptoms. In fact, an efficacious treatment for this complex and multifactorial disorder remains to be discovered, demanding the urgent development of new therapeutic approaches for the disease, such as the use of bioactive secondary metabolites (SMs) from natural sources. Sessile organisms, like plants, are unable to escape from adverse environmental conditions and must therefore create their own defense. Their main defense strategy is chemical defense that includes the production of an enormously diverse array of bioactive SMs, such as terpenes and their derivatives. This largest and most diverse group of plant SMs also provide the treatment of several diseases due to their broad-spectrum bioactivities, for example, anticancer, antioxidant, and anti-inflammatory properties. Thus, the evaluation of the neuroprotective potential of terpenes is imperative. It is known that the major AD clinical indications (CIs) are extracellular senile plaques of amyloid-β (Aβ) protein, intracellular hyperphosphorylated tau (τ) neurofibrillary tangles (NFTs), uncommon neuroinflammatory response, oxidative stress, and synaptic and neuronal dysfunction. Therefore, terpenes that may decrease these CIs might be used for AD treatment. Surely, terpenes targeting more than one AD pathogenic mechanism, multi-target drug ligands (MTDLs), have the potential to become a leading AD treatment. Thus, this review analyzes, for each CI, the scaffolds of the selected terpenes leading to the highest activity.

Bioavailability enhancement of coenzyme Q10: An update of novel approaches.

Coenzyme Q10 (CoQ10) is an essential, lipid-soluble vitamin involved in electron transport in the oxidoreductive reactions of the mitochondrial respiratory chain. Structurally, the quinone ring is connected to an isoprenoid moiety, which has a high molecular weight. Over the years, coenzyme Q10 has become relevant in the treatment of several diseases, like neurodegenerative disorders, coronary diseases, diabetes, hypercholesterolemia, cancer, and others. According to studies, CoQ10 supplementation might be beneficial in the treatment of CoQ10 deficiencies and disorders associated with oxidative stress. However, the water-insoluble nature of CoQ10 is a major hindrance to successful supplementation. So far, many advancements in CoQ10 bioavailability enhancement have been developed using novel drug carriers such as solid dispersion, liposomes, micelles, nanoparticles, nanoemulsions, self-emulsifying drug systems, or various innovative approaches (CoQ10 complexation with proteins). This article aims to provide an update on methods to improve CoQ10 solubility and bioavailability.

Phytochemical analysis and evaluation of antioxidant properties of extracts from leaves, stem-barks and roots of <i>Pterocarpus Erinaceus</i>

Oxidative stress is found to be associated with the etiology of several human diseases. Free radicals are the causative agent of oxidative stress, and can be scavenged by either natural (plants) or synthetic antioxidants. Synthetic antioxidants have some side effects which push a lot of research focuses on natural antioxidants. Pterocarpus erinaceus is a medicinal plant employed as traditional remedy for the treatment of several diseases associated with oxidative stress. This basis, the present study aimed at screening phytochemical and evaluating antioxidant properties of extracts from leaves, stem-barks and roots of Pterocarpus erinaceus. Leaves, stem-barks and roots of Pterocarpus erinaceous after collection were air-dried and pulverized. Each was extracted with methanol and the methanolic extracts were used. Phytochemicals were screened, in vitro, and in vivo antioxidant studies conducted. Rats were grouped into; Group 1: Normal control (liquid paraffin, vehicle 1 ml.kg), Group 2: Negative control (received 1 ml/kg CCl4), Group 3: Positive control (received 1ml/kg CCl4 +1 ml/kg Silymarin), Group 4-6: Extract treated rats (received 1 ml/kg CCl4 + varied doses of Extracts at 100, 200, and 400mg/kg body weight of rats). The treatment was done daily via oral means for 14 days. The results of the study showed Pterocarpus erinaceus rich in different phytochemicals which possess free radicals scavenging properties. In vivo study revealed that Pterocarpus erinaceus could ameliorate CCl4 toxicity in a way that seem to be via elevation of endogenous antioxidant activities. In conclusion, the leaves of Pterocarpus Erinaceus possessed more of the components rich with antioxidant properties hence its recommendation for further study to identify molecules enshrined therein.

Fermented Unripe Plantain Juice Ameliorates Diclofenac-Induced Hepatic and Renal Dysfunction in Wistar Rats

Diclofenac administration has been associated with several health problems in human including gastrointestinal tract problems, renal toxicity, among others. Several medicinal plants are been used locally for the treatment of several diseases. The aim of this study was to investigate the potential of fermented unripe plantain juice (FUPJ) in ameliorating diclofenac-induced ulcer and renal dysfunction. Twenty (20) healthy adult Wister rats weighing between 110g to 200g were randomly divided into four groups of five rats each. Group I served as control, received distilled water and feeds, Group 2 received 10mg/kg body weight of diclofenac only, Group 3 received 10mg/kg body weight of diclofenac only and post treated with 200mg/kg body weight of FUPJ and Group 4 received 200mg/kg body weight of FUPJ. The diclofenac was administered IP and fermented unripe plantain extract was administered orally for fourteen (14) days. The results showed that diclofenac administration caused a significant increase (p<0.05) in serum levels of creatinine and a significant decrease (p<0.05) in antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) compared to the control group. Additionally, diclofenac administration caused ulceration in the gastric mucosa. However, treatment with FUPJ significantly reduced (p<0.05) the levels of creatinine, urea, and MDA and increased (p<0.05) the levels of antioxidant enzymes in a dose-dependent manner. The highest dose of FUPJ (200mg/kg) showed the most significant reduction in the levels of the tested parameters and prevented the gastric mucosal ulceration. In conclusion, FUPJ has the potential to ameliorate diclofenac-induced ulcer and renal dysfunction through its antioxidant and anti-inflammatory properties.

The Effect of Cell Culture Passage on the Efficacy of Mesenchymal Stromal Cells as a Cell Therapy Treatment.

Background/Objective: Mesenchymal Stromal Cells (MSCs) have been considered a promising treatment for several diseases, such as cardiac injuries. Many studies have analyzed their functional properties; however, few studies have characterized MSCs through successive culture passages. The main objective of this work was to analyze the phenotype and functionality of MSCs isolated from two different sources in five culture passages to determine if the culture passage might influence the efficacy of MSCs as a cell therapy treatment. Methods: Bone Marrow (BM)-MSCs were harvested from the femur of Wistar rats (n = 17) and Adipose Tissue(AT)-MSCs were isolated from inguinal fat (n = 17). MSCs were cultured for five culture passages, and the immunophenotype was analyzed by flow cytometry, the functionality was characterized by adipogenic, osteogenic, and chondrogenic differentiation assays, and cytokine secretion capacity was determined through the quantification of the Vascular Endothelial Growth-Factor, Fibroblast Growth-Factor2, and Transforming Growth-Factorβ1 in the cell supernatant. The ultrastructure of MSCs was analyzed by transmission electron microscopy. Results: BM-MSCs exhibited typical phenotypes in culture passages two, four, and five, and their differentiation capacity showed an irregular profile throughout the five culture passages analyzed. AT-MSCs showed a normal phenotype and differentiation capacity in all the culture passages. BM- and AT-MSCs did not modify their secretion ability or ultrastructural morphology. Conclusions: Throughout the culture passages, BM-MSCs, but not AT-MSCs, exhibited changes in their functional and phenotypic characteristic that might affect their efficacy as a cell therapy treatment. Therefore, the culture passage selected should be considered for the application of MSCs as a cell therapy treatment.

Mechanistic insights into the hepatoprotective properties of Mallotus phillipensis fruit: Targeting proinflammatory cytokines and free radicals using isolated compound

Ethnopharmacological relevance:Mallotus phillipensis (MP) belongs to the endangered plants of great medicinal value. Widely used in the Ayurvedic healthcare system, parts of the plant which are rich in secondary metabolites are used in the treatment of several diseases like eczema, bronchitis, worm infestation, diabetes, kidney stones, cancer, and malaria. In ethnomedicine, MP has been reported to be traditionally used in the treatment and healing of jaundice and inflammatory conditions in the Ayurveda system. This plant was thus selected to explore its hepatoprotective activity. ObjectiveThis study was undertaken to investigate the protective property of MP and a flavanone i.e. 7,4′-Dihydroxy-3′′,3′′-dimethyl-(5,6-pyrano-2′′-one)-8′′′-(3′′′,3′′′-dimethylallyl)-flavanone (A4) previously identified and obtained from the same plant on CCl4-induced liver injury in animal models to validate the folkloric claims. Traditional medicinal plants have the potential to provide phytoconstituents capable of healing liver cells. In this regard, MP is used in various traditional medicinal systems to treat several diseases. Though it has been studied for its hepatoprotective potential, activity on the isolated compounds is yet to be reported to confirm the active principle. Therefore, the study assessed the hepatoprotective effect of ethyl acetate and methanol extracts and a flavanone isolated from MP fruit extract. MethodsMethanol and ethyl acetate fractions of MP fruits at two different doses (300 mg/kg and 500 mg/kg) and a flavanone (A4-50 mg/kg) isolated from MP were tested for hepatoprotective potential in rats. At 50 mg/kg dosage/ day orally, silymarin was used as a standard drug. The effect on liver enzymes and serum cytokines was also verified in animal models. Histopathology and antioxidant tests were performed on liver tissue. Elemental analysis, 1H- &13C NMR, MS, IR and UV spectral data were used to characterize the structure of isolated flavanone (A4). ResultsThe ethyl acetate and methanol fractions of MP fruit and the isolated compound A4 i.e. flavanone showed strong hepatoprotective effects, as evidenced by their ability to impede the rise in serum transaminases. They also decreased the serum IL-1, IL-6 and TNF-α levels and showed significant antioxidant potential. The effect was found to be in decreasing order as MEA 500 > MPM 500 > MEA 300 > A4 > MPM 300. ConclusionsThe results indicate that MP fruit fractions with methanol, ethyl acetate and A4 can lessen CCL4-induced liver damage. This may be because of their antioxidant and cytokine-inhibitory properties.

Study of mass and heat transfer for peristaltic transport of cross nanofluid through a curved channel

AbstractNanoparticles have significant applications in drug delivery systems, heat exchanges, treatment of several diseases and chemical reactions. The Cross non‐Newtonian nanofluid model for heat and mass transfer inspection with diethylene glycol‐based fluid is highlighted in this study. The magnesium aluminate nanoparticles are used to evaluate nanofluid characteristics. The current investigation explores the numerical results for magnetohydrodynamics (MHD) peristaltic movement of Cross‐nanofluid via a curved channel under the influences of thermal radiation, heat sink/source and Joule heating. The effects of viscous dissipation, thermophoretic, variable thermal conductivity and Brownian diffusion coefficients in the presence of mass and thermal convection are also taken into consideration. Flow problem is modeled using fundamental conservation laws, and the resulting nonlinear partial differential equations (PDEs) are reduced to a system of nonlinear ordinary differential equations (ODEs) by employing long wavelength and a small Reynolds number approximations. Simplified systems of ODEs are addressed by adopting numerical technique via the NDSolve built‐in command in Mathematica. Furthermore, graphical presentations explain the behavior of relevant flow parameters. Results indicate that better values of the magnetic number and the thermophoresis parameter increase the rate of mass transfer. Results indicate that the nanofluid's temperature increases by improving values of the Brinkman number and falls with the thermal radiation parameter. It is also stated that the nanofluid's velocity reduces near the lower wall for greater values of Hartman number. Moreover, heat transfer rate improves for larger values of the heat generation parameter and curvature parameter.

Berberine: Pharmacological Features in Health, Disease and Aging.

Berberine is the main active compound of different herbs and is defined as an isoquinoline quaternary botanical alkaloid found in barks and roots of numerous plants. It exhibits a wide range of pharmacological effects, such as anti-obesity and antidiabetic effects. Berberine has antibacterial activity against a variety of microbiota, including many bacterial species, protozoa, plasmodia, fungi, and trypanosomes. This review describes the role of berberine and its metabolic effects. It also discusses how it plays a role in glucose metabolism, fat metabolism, weight loss, how it modulates the gut microbiota, and what are its antimicrobial properties along with its potential side effects with maximal tolerable dosage. Representative studies were considered and analyzed from different scientific databases, including PubMed and Web of Science, for the years 1982-2022. Literature analysis shows that berberine affects many biochemical and pharmacological pathways that theoretically yield a positive effect on health and disease. Berberine exhibits neuroprotective properties in various neurodegenerative and neuropsychological ailments. Despite its low bioavailability after oral administration, berberine is a promising tool for several disorders. A possible hypothesis would be the modulation of the gut microbiome. While the evidence concerning the aging process in humans is more limited, preliminary studies have shown positive effects in several models. Berberine could serve as a potential candidate for the treatment of several diseases. Previous literature has provided a basis for scientists to establish clinical trials in humans. However, for obesity, the evidence appears to be sufficient for hands-on use.

Allele-specific antisense oligonucleotides for the treatment of BEST1-related dominantly inherited retinal diseases: An in vitro model

Retinal dystrophies are a common health problem worldwide that are currently incurable due to the inability of retinal cells to regenerate. Inherited retinal diseases (IRDs) are a diverse group of disorders characterized by progressive vision loss caused by photoreceptor cell dysfunction. The eye has always been an attractive organ for the development of novel therapies due to its independent access to the systemic pathway. Moreover, anti-sense oligonucleotides (ASOs), which facilitate manipulation of unwanted mRNAs via degradation or splicing, are undergoing rapid development and have been clinically deployed for the treatment of several diseases. The primary aim of this study was to establish a reliable in vitro model utilizing induced photoreceptor-like cells (PRCs) for assessing the efficacy and safety of ASOs targeting the BEST1 gene. Despite advances in gene therapy, effective treatments for a broad range of IRDs remain limited. An additional aim was to develop an in vitro model for evaluating RNA-based therapeutics, specifically ASOs, for the treatment in IRDs.Firstly, a cell culture model was established by induction of PRCs from dermal fibroblasts via direct programming. The induced PRCs were characterized at both the transcriptomic and protein level. Then, a common single nucleotide polymorphism (SNP) was identified in the BEST1 gene (rs1800007) for targeting with ASOs. ASOs were designed using the GapmeR strategy to target multiple alleles of this SNP, which is potentially suitable for a large proportion of the population. The efficacy and possible off-target effects of these ASOs were also analyzed in the induced PRC model.The findings show that the selected ASOs achieved allele-specific mRNA degradation with virtually no off-target effects on the global transcriptome profile, indicating their potential as safe and effective therapeutic agents. The presented in vitro model is a valuable platform for testing personalized IRD treatments and should inspire further research on RNA-based therapeutics. To the best of our knowledge this study is the first to test RNA-based therapeutics involving the use of ASOs in an induced PRC model. Based on the present findings, it will be possible to establish an ex vivo disease model using dermal fibroblast samples from affected individuals. In other words, the disease model and the ASOs that were successfully designed in this study can serve as a useful platform for the testing of personalized treatments for IRDs.

Synthesis and biological evaluation of 3‐hydroxypyrazoles as aquaporin 9 inhibitors

AbstractA series of 3‐hydroxypyrazole derivatives have been synthesized by a base‐promoted reaction of nitro‐substituted donor–acceptor cyclopropanes with hydrazines. The synthesized compounds have been investigated for their ability to inhibit aquaporin 9 (AQP9) in rat Leydig cells (LC‐540). The protein data bank structure for AQP9 was predicted using homology modeling; and the protein–ligand interaction for the synthesized hydroxyl pyrazole derivatives were analyzed using molecular modeling and docking studies. The results of in silico analyses showed that compound 5b had a higher binding affinity with AQP9 than other compounds. Further, in vitro studies conducted in LC‐540 cells confirmed that compound 5b effectively inhibits AQP9. Hence, compound 5b may be used as an inhibitor in enhancing our understanding of AQP9 function, and in the treatment of several diseases.

Melissa officinalis extract palliates redox imbalance and inflammation associated with hyperthyroidism-induced liver damage by regulating Nrf-2/ Keap-1 gene expression in γ-irradiated rats

BackgroundMelissa officinalis (MO) is a well-known medicinal plant species used in the treatment of several diseases; it is widely used as a vegetable, adding flavour to dishes. This study was designed to evaluate the therapeutic effect of MO Extract against hyperthyroidism induced by Eltroxin and γ-radiation.MethodsHyperthyroidism was induced by injecting rats with Eltroxin (100 µg/kg/ day) for 14 days and exposure to γ-radiation (IR) (5 Gy single dose). The hyperthyroid rats were orally treated with MO extract (75 mg/kg/day) at the beginning of the second week of the Eltroxin injection and continued for another week. The levels of thyroid hormones, liver enzymes and proteins besides the impaired hepatic redox status and antioxidant parameters were measured using commercial kits. The hepatic gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its inhibitor Kelch-like ECH-associated protein-1(Keap-1) in addition to hepatic inflammatory mediators including tumor necrosis factor-α (TNF- α), Monocyte chemoattractant protein-1 (MCP-1) and fibrogenic markers such as transforming growth factor-beta1 (TGF-β1) were determined.ResultsMO Extract reversed the effect of Eltroxin + IR on rats and attenuated the thyroid hormones. Moreover, it alleviated hyperthyroidism-induced hepatic damage by inhibiting the hepatic enzymes’ activities as well as enhancing the production of proteins concomitant with improving cellular redox homeostasis by attenuating the deranged redox balance and modulating the Nrf2/Keap-1 pathway. Additionally, MO Extract alleviated the inflammatory response by suppressing the TNF- α and MCP-1 and prevented hepatic fibrosis via Nrf2-mediated inhibition of the TGF-β1/Smad pathway.ConclusionAccordingly, these results might strengthen the hepatoprotective effect of MO Extract in a rat model of hyperthyroidism by regulating the Nrf-2/ Keap-1 pathway.

Put on the sidelines of palliative care: a qualitative study of important barriers to GPs’ participation in palliative care and guideline implementation in Norway

Background Demographic changes, the evolvement of modern medicine and new treatments for severe diseases, increase the need for palliative care services. Palliative care includes all patients with life-limiting conditions, irrespective of diagnosis. In Norway, palliative care rests on a decentralised model where patient care can be delivered close to the patient’s home, and the Norwegian guideline for palliative care describes a model of care resting on extensive collaboration. Previous research suggests that this guideline is not well implemented among general practitioners (GPs). In this study, we aim to investigate barriers to GPs’ participation in palliative care and implementation of the guideline. Methods We interviewed 25 GPs in four focus groups guided by a semi-structured interview guide. The interviews were recorded and transcribed verbatim. Data were analysed qualitatively with reflexive thematic analysis. Results We identified four main themes as barriers to GPs’ participation in palliative care and to implementation of the guideline: (1) different established local cultures and practices of palliative care, (2) discontinuity of the GP–patient relationship, (3) unclear clinical handover and information gaps and (4) a mismatch between the guideline and everyday general practice. Conclusion Significant structural and individual barriers to GPs’ participation in palliative care exist, which hamper the implementation of the guideline. GPs should be involved as stakeholders when guidelines involving them are created. Introduction of new professionals in primary care needs to be actively managed to avoid inappropriate collaborative practices. Continuity of the GP–patient relationship must be maintained throughout severe illness and at end-of-life.

Microfluidic nanoparticle synthesis for oral solid dosage forms: A step toward clinical transition processes

Nanomedicine provides various opportunities for addressing medical challenges associated with drug bioavailability, stability, and efficacy. In particular, oral nanoparticles (NPs) represent an alternative strategy to enhance the solubility and stability of active ingredients through the gastrointestinal tract. The nanocarriers could be used for both local and systemic targeting, enabling controlled release of encapsulated drugs. This approach allows more efficient therapies.In this work, we aim to develop reliable oral solid dosage forms incorporating NPs produced by either one pot synthesis or continuous production, following protocols that yield highly consistent outcomes, promoting their technology transfer and clinical use.Microfluidics technology was selected to allow an automated and highly productive synthetic approach suitable for the highly throughput production.In particular, innovative systems, which combine advantage of NPs and solid dosage formulation, were designed, developed, and characterized demonstrating the possibility to obtaining oral administration. The resulting NPs were thus carried on oral dosage forms, i.e., pellets and minitablets. NPs resulted stable after dosage forms manufacturing, leading to confidence also on protection of encapsulated drugs. Indomethacin was used as a tracer to test biopharmaceutical behaviour.Anti-inflammatories or cytotoxic chemotherapeutics could be vehiculated leading to a breakthrough in the treatment of severe diseases allowing the oral administration of these drugs. We believe that the advancement achieved with the results of our work paves the way for the progression of nanoproducts into clinical transition processes.

Exploring the Fascinating Diversity, Medicinal Significance, and Ecological Adaptation of Ceropegia bulbosa Roxb.: A Comprehensive Review

Background: A large variety of unknown plants has tremendous usefulness in improving human beings from a medicinal, nutritional, and dietary perspective. Ceropegia bulbosa species are threatened plant species by (the International Union for Conservation of Nature) IUCN which have significant medicinal value. Ceropegia bulbosa species are generally found in various regions of India. GC-MS data of different extracts such as Ethanol, Methanol, Acetone, Ethyl acetate, and chloroform show the biologically active compounds that exhibit various biological actions. Bioactive compounds reported in Ceropegia bulbosa are Tetradecanoic acid, Pentadecanoic acid, Heptadecanoic acid, Octadecanoic acid, Ergost-5-en-3-ol, (3 beta, 24R)- Stigmast-5-en-3-ol, Tetracontane, Squalene, Beta-stigmasterol. Discussion: Traditionally, leaves, tubers, stems, and flowers are used in the treatment of several diseases. Also, various tribal and rural regions have a different identity of Ceropegia bulbosa. Hence, it has the same ethnopharmacological remedies like the decoction of tubers used to treat dysentery and diarrhea and remove kidney stones. Pulp of leaves used for deafness. Conclusion: Traditionally, it is used as an anti-urolithic, dysentery and diarrhea, deafness, and fertility enhancer. The plant is reported as anti-urolithic, anti-fungal, anti-oxidant, immunomodulatory, malnutrition, and Balya karma. Ceropegia bulbosa is reported to contain Tetradecanoic acid, Pentadecanoic acid, Heptadecanoic acid, Octadecanoic acid, Ergost-5-en-3-ol, (3 beta, 24R)-Stigmast-5-en-3-ol, Tetracontane, Squalene, Beta-stigmasterol.

In silico ADMET and anti-inflammatory profiles of the stigmast-4-en-3-one and isolation of isovanillin as the antioxidant principle of Imperata cylindrica (L.) P. Beauv

Imperata cylindrica (L.) P. Beauv. is an invasive species widely used in treatment of several diseases associated with pain and inflammation in different countries including Madagascar. This work aims to report the isolation of the antioxidant, analgesic and anti-nflammatory compounds from the methanol extract of I. cylindrica. The bio-guided method was used to isolate its bioactive compounds by combining chromatographic methods, writhing test in mice and antioxidant assays. Stigmast-4-en-3-one was isolated as one among the compounds responsible for the analgesic and anti-inflammatory properties and isovanillin as one among the antioxidant compounds from the extract. Stigmast-4-en-3-one showed a good oral pharmacokinetic profile and good binding affinities with some pro-inflammatory targets. It did not show any mutagenic effect, nor a carcinogenic one and had a low risk to be a cardiotoxic agent. All of our results provide scientific justification for its traditional medicinal use in the management of pain and inflammatory related diseases.

Personalized inference for neurostimulation with meta-learning: a case study of vagus nerve stimulation.

Objective. Neurostimulation is emerging as treatment for several diseases of the brain and peripheral organs. Due to variability arising from placement of stimulation devices, underlying neuroanatomy and physiological responses to stimulation, it is essential that neurostimulation protocols are personalized to maximize efficacy and safety. Building such personalized protocols would benefit from accumulated information in increasingly large datasets of other individuals' responses.Approach. To address that need, we propose a meta-learning family of algorithms to conduct few-shot optimization of key fitting parameters of physiological and neural responses in new individuals. While our method is agnostic to neurostimulation setting, here we demonstrate its effectiveness on the problem of physiological modeling of fiber recruitment during vagus nerve stimulation (VNS). Using data from acute VNS experiments, the mapping between amplitudes of stimulus-evoked compound action potentials (eCAPs) and physiological responses, such as heart rate and breathing interval modulation, is inferred.Main results. Using additional synthetic data sets to complement experimental results, we demonstrate that our meta-learning framework is capable of directly modeling the physiology-eCAP relationship for individual subjects with much fewer individually queried data points than standard methods.Significance. Our meta-learning framework is general and can be adapted to many input-response neurostimulation mapping problems. Moreover, this method leverages information from growing data sets of past patients, as a treatment is deployed. It can also be combined with several model types, including regression, Gaussian processes with Bayesian optimization, and beyond.