Low Dose Research Articles

Uptitration of Sacubitril/Valsartan and Outcomes in Patients With Heart Failure - Insight From the REVIEW-HF Registry.

Guideline-directed medical therapy has become an important component of heart failure (HF) therapy, with sacubitril/valsartan as one of the recommended drugs; however, the real-world prognostic implications of sacubitril/valsartan uptitration are unclear. Patients with HF newly initiated on sacubitril/valsartan were registered in a retrospective multicenter study (REVIEW-HF). In all, 995 patients were divided into 3 groups according to the maximum dose achieved: high dose, sacubitril/valsartan 400 mg; intermediate dose, sacubitril/valsartan 200-<400 mg; and low dose, sacubitril/valsartan <200 mg. A total of 397 (39.9%) patients received high-dose sacubitril/valsartan; they had a significantly lower risk of mortality or HF hospitalization than patients in the low-dose (hazard ratio [HR] 0.39; 95% confidence interval [CI] 0.29-0.53; P<0.001) and intermediate-dose (HR 0.64; 95% CI 0.45-0.94; P=0.03) groups. In the multivariable Cox regression model, higher systolic blood pressure and maintained geriatric nutritional risk index were significantly associated with a higher incidence of achieving a high dose of sacubitril/valsartan. Patients who did not receive high-dose sacubitril/valsartan experienced more hypotension during the follow-up period, whereas hyperkalemia, severe renal events, and angioedema did not differ across the achieved dose classifications. Patients who achieved sacubitril/valsartan uptitration had a better prognosis than those who did not. Before sacubitril/valsartan uptitration, patients need to monitor blood pressure closely to prevent worsening events.

Unlocking full potential of bamboo waster: Efficient co-production of xylooligosaccharides, lignin, and glucose through low-dosage mandelic acid hydrolysis with alkaline processing.

Mandelic acid (MA), a natural and environmentally friendly organic acid, demonstrates high selectivity and efficiency in hydrolyzing hemicellulose, making it an excellent candidate for xylooligosaccharides (XOS) production at low acid dosages. Despite its potential, the application of MA for XOS production has not been evaluated. The study first investigated the effectiveness of MA in hydrolyzing hemicellulose in bamboo into XOS. Under optimized conditions (50 mM MA, 180 °C, 45 min), a high XOS yield of 65.9 % was achieved, with a total xylobiose and xylotriose yield of 43.5 %. Subsequent alkaline pretreatment enabled 92.1 % lignin removal from MA-pretreated bamboo. The recovered lignin exhibited a high purity of 95.2 % and retained fundamental structure and functional groups of native lignin. The resulting residue displayed enhanced crystallinity and accessibility, with reduced hydrophobicity and surface area lignin compared to untreated bamboo. At high substrate concentration of 20 %, cellulase hydrolysis resulted in a glucose conversion efficiency of 83.9 %. Overall, this integrated strategy offered an efficient approach for the co-production of valuable XOS, lignin, and glucose from bamboo. The efficient energy utilization and economic viability further highlight the potential of this method for large-scale industrial applications, making it an attractive option for biomass valorization.

The Role of CT and MR Imaging in Stereotactic Body Radiotherapy of the Spine: From Patient Selection and Treatment Planning to Post-Treatment Monitoring

Spine metastases (SMs) are common, arising in 70% of the cases of the most prevalent malignancies in males (prostate cancer) and females (breast cancer). Stereotactic body radiotherapy, or SBRT, has been incorporated into clinical treatment algorithms over the past decade. SBRT has shown promising rates of local control for oligometastatic spinal lesions with low radiation dose to adjacent critical tissues, particularly the spinal cord. Imaging is critically important in SBRT planning, guidance, and response monitoring. This paper reviews the roles of imaging in spine SBRT, including conventional and advanced imaging approaches for SM detection, treatment planning, and post-SBRT follow-up.

Sodium carbonate pulping of oil palm empty fruit bunches for paperboard production

Abstract This study investigated the use of sodium carbonate pulping in oil palm empty fruit bunch (OPEFB) pulp production for paperboard manufacturing. The pulping varying the active alkali (AA) (4.5 %, 6.5 %, 8.5 %), NaOH fraction (F) (10 %, 20 %, 30 %), and cooking time (T) (30′, 60′, 90′). The performance was evaluated based on screened pulp yield, kappa number, and delignification selectivity. Furthermore, the functional groups, S/G ratio, and morphological structure of the optimum pulp were observed. The tensile and tear indices of the OPEFB pulp paperboard were also measured. The results suggest sodium carbonate pulping at a low chemical dose successfully produced OPEFB pulp. Based on the highest delignification selectivity value of 12.74, the most effective pulping conditions were achieved with AA-6.5 %, F-30 %, and T-90′. The optimum OPEFB pulp analysis revealed a decrease in lignin proportion with the dominant degradation of the syringyl unit. Thus, the fibers are easily separable during mechanical treatment. These characteristics influenced the paperboard, resulting high tensile and tear indices of 7.90–8.15 Nm g−1 and 15.09–16.25 mN m2 g−1, respectively. Overall, this study demonstrated the potential of sodium carbonate pulping to produce high-quality pulp and paperboard from OPEFBs, highlighting the thoroughness of the research process in the pulp and paper manufacturing field.

Lysine deacetylase inhibitors have low selectivity in cells and exhibit predominantly off-target effects.

Lysine deacetylases (KDACs or HDACs) are metal-dependent enzymes that regulate lysine acetylation, a post-translational modification that is present on thousands of human proteins, essential for many cellular processes, and often misregulated in diseases. The selective inhibition of KDACs would allow for understanding of the biological roles of individual KDACs and therapeutic targeting of individual enzymes. Recent studies have suggested that purportedly specific KDAC inhibitors have significant off-target binding, but the biological consequences of off-target binding were not evaluated. We compared the effects of treatment with two of the reportedly most KDAC-selective inhibitors, Tubastatin A and PCI-34051, in HT1080 cells in which the endogenous KDAC6 or KDAC8 gene has been mutated to inactivate enzyme catalysis while retaining enzyme expression. Genetic inactivation results in much stronger deacetylation defects on known targets compared to inhibitor treatment. Gene expression analysis revealed that both inhibitors have extensive and extensively overlapping off-target effects in cells, even at low inhibitor doses. Furthermore, Tubastatin A treatment led to increased histone acetylation, while inactivation of KDAC6 or KDAC8 did not. Genetic inactivation of KDAC6, but not KDAC8, impaired tumor formation in a xenograft model system, in contrast to previous reports with KDAC inhibitors suggesting the reverse. We conclude that the majority of observed biological effects of treatment with KDAC inhibitors are due to off-target effects rather than the intended KDAC inhibition. Developing a truly specific KDAC6 inhibitor could be a promising therapeutic avenue, but it is imperative to develop new inhibitors that selectively mimic genetic inactivation of individual KDACs.

Metabolic impact of low dose IL-2 therapy for primary Sjögren's Syndrome in a double-blind, randomized clinical trial.

Low-dose interleukin 2 (Ld-IL2) is increasingly being explored as an immune-modulating treatment for autoimmune diseases which mainly affect T cell subsets. This study investigates the metabolic effects of Ld-IL2 therapy in patients with primary Sjögren's syndrome (pSS). A total of 60 patients were recruited to conduct a double-blind, randomized clinical trial. Of these patients, 50% (30/60) received Ld-IL2 therapy along with standard treatment for 12 weeks, followed by 12 weeks of follow-up. The effectiveness was evaluated by Sjögren's Tool for Assessing Response (STAR). An untargeted analysis was performed to profile hydrophilic metabolites. Metabolic profiling revealed significant alterations post-treatment, notably in metabolites like acetyl-CoA, ascorbic acid, and glutathione, which are beneficial in managing autoimmune diseases. In addition, the levels of metabolite accumulation were correlated with variations in immune cell subsets (p< 0.05), particularly Tregs. Moreover, patients exhibiting a specific metabolic profile, including lower serum levels of isoleucine, ADP, Thymidine 5'-triphosphate, and other metabolites, had a high response rate (91.7%-98.6%), as indicated by the receiver operating characteristic (ROC) curve. These findings suggest that Ld-IL2 therapy influences metabolic pathways in pSS, offering insights into the systemic effects of Ld-IL2 therapy beyond immune modulation. ClinicalTrials.gov number, NCT02464319. Key Points •Metabolic alteration in pSS is significantly associated with Ld-IL2 therapy. •Metabolic changes correlate with variations in immune cell subsets, particularly Tregs. •Metabolic profiling could be a valuable tool in guiding Ld-IL2 therapy choices for pSS patients.

Effect of BTHWA Biostimulation on Lettuce Using Chlorophyll Fluorescence, Gas Exchange, and Thermography

The aim of this study was to examine lettuce using different concentrations of the biostimulator N-methyl-N-methoxyamide-7-carboxybenzo(1.2.3)thiadiazole (BTHWA), a new benzothiadiazole derivative. Different concentrations of BTHWA during watering and spraying were applied to lettuce. Chlorophyll fluorescence, gas exchange, thermal images, and plant parameter data were used to study physiological process and the growth of lettuce. Chlorophyll fluorescence data showed a strong effect after the first BTHWA application to lettuce. After three applications, the plants were harvested and data were recorded. Similarly, in the second experiment, gas exchange and thermal images were recorded after the first treatment of BTHWA. Our findings showed improved chlorophyll efficiency after the first BTHWA application, and no adverse effects were recorded on the overall photochemistry at any concentration. Regarding growth parameters, spraying BTHWA reduced the fresh weight but decreased the damage index. A lower watering concentration (0.066 mg/L) applied three times did not cause any damage to plants and fresh weight, even after repeated applications. Infrared thermal images showed BTHWA application also significantly affected plant temperature. Gas exchange data revealed that sprayed plants exhibited higher transpiration rates, stomatal conductance, and photosynthetic rates when compared to watered and control plants. This study suggests that application of a low dose of BTHWA is safe to use in agriculture practices in lettuce without compromising its growth and yield.

Phytoecdysteroids: Quantification in Selected Plant Species and Evaluation of Some Effects on Gastric Smooth Muscles

Phytoecdysteroids (PEs) are naturally occurring steroid compounds, that have recently gained significant attention, due to their diverse biological activities and high therapeutic potential. The aim of the present study was to quantify some PEs including 20-hydroxyecdysterone (20-HE), ponasterone A (PA), and turkesterone (TU) in selected plant foods and Rhaponticum carthamoides extract. Furthermore, the effects of 20-HE, TU, and R. carthamoides extract, were investigated with in vitro methods using isolated smooth muscle tissues. The levels of 20-HE in the analyzed samples exhibited significant differences, with kaniwa seed extract containing the highest amount, followed by spinach leaf extract, quinoa seed extract, and asparagus stem extract. The in vitro analyses suggested that R. carthamoides extract exhibits dose-dependent cytotoxic effects on smooth muscle cells, with low doses promoting contraction and higher doses inducing relaxation. Additionally, the extract demonstrated a significant inhibitory effect on ACh-induced contractions, while 20-HE enhanced the contractile response. The current findings highlighted phytoecdysteroids’ potential for modifying gastrointestinal motility.

Effect of Oral Administration of Collagen Peptide OG-5 on Advanced Atherosclerosis Development in ApoE−/− Mice

Background/Objectives: Atherosclerosis is a chronic inflammatory disease of the arterial wall, which involves multiple cell types. Peptide OG-5 is identified from collagen hydrolysates derived from Salmo salar and exhibits an inhibitory effect on early atherosclerosis. The primary objective of this study was to investigate the impact of OG-5 on advanced atherosclerotic lesions as well as its stability during absorption. Methods: In this study, the ApoE-/- mice were employed to establish advanced atherosclerosis model to investigate the treatment effect of peptide OG-5. Results: The results showed that oral administration of OG-5 at a dosage of 150 mg/kg bw resulted in a 30% reduction in the aortic plaque formation area in ApoE−/− mice with few bleeding risks. Specifically, intervention with a low dose of OG-5 (50 mg/kg bw), initiated in the early stage of atherosclerosis, continues to provide benefits into the middle and late stages without bleeding risks. Furthermore, treatment of OG-5 increased expression levels of contractile phenotype markers and reduced the accumulation of lipoprotein in VSMCs induced by ox-LDL. Peptide OG-5 could ensure transport across Caco-2 cell monolayers, exhibiting a Papp value of 1.80 × 10−5 cm/s, and exhibited a robust stability in plasma with remaining content &gt;70% after 8 h incubation. In vivo studies revealed that OG-5 reached maximum concentration in blood after 120 min. Conclusion: The present results demonstrate the potential efficacy of peptide OG-5 as a promising agent for intervention in anti-atherogenesis strategies.

Continuous infusion of piperacillin/tazobactam optimizes intraoperative antibiotic exposure in patients undergoing elective pelvic exenteration surgery.

Patients undergoing elective pelvic exenteration surgery who receive piperacillin/tazobactam as surgical prophylaxis are at risk of suboptimal intraoperative antibiotic exposure. With this work, we aimed to study the plasma pharmacokinetics of piperacillin and tazobactam in this population to provide dosing recommendations that optimize antibiotic exposure. We developed a prospective, observational, pharmacokinetic study of piperacillin/tazobactam in patients undergoing pelvic exenteration. Population pharmacokinetic analysis and Monte Carlo simulations were performed with Monolix and Simulx software. Probabilities of target attainment of different dosing regimens against the minimum inhibitory concentration (MIC) breakpoints (8 and 16 mg/L) were calculated. Twelve patients were included in the study, with a median age of 50.0 years [interquartile interval (45.3-57.5)] and a median weight of 79.0 kg (61.3-88.3). Median surgical time was 10.5 h (9.8-11.7). A two-compartment linear model best fitted piperacillin and tazobactam data (190 plasma samples). Monte Carlo simulations showed that a lower dose of 2 g/0.25 g loading dose followed by 4 g/0.5 g q8h by continuous infusion provided ≥90% probability of target attainment for MIC = 16 mg/L for most of the patients. For non-continuous infusion regimens, only the 2-hourly bolus re-dosing achieved intraoperative concentrations of piperacillin ≥16 mg/L. Patients with weights ≥ 100 kg and glomerular filtration rates ≥ 120 mL/min required 4 g/0.5 g q6h by continuous infusion after a loading dose. In conclusion, continuous infusion of lower doses of piperacillin/tazobactam is as adequate as the 2-hourly re-dosing recommended by the current guidelines for surgical prophylaxis in pelvic exenteration. Patients with higher weights and glomerular filtration rates are at greater risk of inadequate exposure.

Determination of Astrocyte Reaction Using Glial Fibrillary Acidic Protein (GFAP) Following Aluminium Chloride Induced Hippocampus Damage of Adult Wistar Male Rats Treated with Ethanolic Extracts of Carpolobia lutea at Different Doses

Background: Aluminium is a well-established neurotoxicant involved in the etiology of neurodegenerative diseases. Carpolobia lutea, commonly called cattle stick or poor man’s candle belongs to the plant family polygalaceae. It is a small tree native to West and Central tropical Africa and it is one of the medicinal plants that play a major role in the health care system of developing countries such as Nigeria. Aim of the Study: This study was aimed at investigating astrocyte reaction in aluminium chloride induced neurotoxicity in the hippocampus in adult male wistar rats treated with ethanolic extracts of C.lutea at different doses. Materials and Methods: Thirty wistar rats weighing 180-200 g were used for this study. The animals were randomized into five groups of six rats each. Group A rats received only animal feed. Groups B,C,D and E were given 100 mg/kg bw of aluminium chloride intraperitoneally five times a week for three weeks to induce neurotoxicity.In order to reverse the neurotoxicity,. Group C was treated with 10 mg/kg bw of donepezil as standard drug while group D and E were treated with 200 mg/kg and 400 mg/kg of Carpolobia lutea respectively for 14 days. Histopathological study was done on the hippocampus of the rat brain and thereafter hematoxylin and eosin staining were carried out. Immunohistochemical studies for GFAP was done using NovocasraTM Novolink TMpolymer detection system and appropriate primary monoclonal antibodies. Image J cell counter tool was used to note the number of GFAP positive cells across all groups. Results: The result from our histopatholological study shows that lower dose (200 mg/kg/bw) of ethanolic extract of the leaf of Carpolobia lutea have better protection on the cytoarchitecture of the CA1, CA3, and dentate gyrus of the hippocampus than 400 mg/kg/bw of the plant extract. From our study, it is evident that 200 mg/kg of Carpolobia lutea reduced the GFAP immunoreactivity in the hippocampus of AlCl3 induced neurotoxicity. When we compared the result of 200 mg/kg/bw of C. lutea with 10 mg/kg per body weight of donepezil (standard drug), it was observed that C. lutea had a slight reduced GFAP immunoreactivity than the standard drug(donepezil). The lower dose, 200 mg/kg of ethanolic extract of the leaf of Carpolobia lutea have a better neuroprotective benefit than the standard drug on the hippocampus Conclusion: In conlusion, 200 mg/kg of Carpolobia lutea have the tendencies of protecting the neurons in the hippocampus from degenerating as a result of aluminium chloride induced neurotoxicity compared to the standard drug (10 mg/kg donepezil).

Evaluation of the antibacterial potential of mango (Mangifera indica) seed kernels in Bangladesh

Antimicrobial resistance is a global threat. On the other hand, Bangladesh produces high-quality mangoes, yet the mango coat and seed kernel, which contain medicinal components, remain unused. Therefore, this study investigated the antibacterial potential and toxicity of ethanol extracts from mango (Mangifera indica) seed kernels, which specifically target the bacterial strains Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Klebsiella sp. Amrapali variant mango seeds were collected, dried, ground into a fine powder, and extracted with ethanol at various ratios. The efficacy of the crude extract was tested via the disc diffusion method. The results demonstrated significant antibacterial activity against gram-positive bacteria (S. aureus and B. cereus), with clear zones of inhibition observed, especially in a dose-dependent manner. The pure crude extract inhibited the growth of S. aureus with a zone of 23 mm, identical to that produced by doxycycline. However, the extract exhibited limited activity against gram-negative bacteria (E. coli and Klebsiella sp.). Additionally, the extract was effective against multidrug-resistant S. aureus. The pure crude extract produced a 22.5 mm zone of inhibition against multidrug-resistant S. aureus, which was slightly smaller than that of gentamicin (23 mm) but larger than those of chloramphenicol (21 mm), vancomycin (20 mm), and tetracycline (16 mm). In vivo toxicity was assessed in mice, revealing no significant adverse effects on the hepatic structure or renal cortex at lower doses (100 μl of pure crude extract). However, higher doses caused mild histopathological changes in the liver and kidneys. These findings suggest that mango seed kernel extract holds promise as an alternative antibacterial agent, particularly against gram-positive and antibiotic-resistant bacteria, while being relatively safe at lower doses. Further research is needed to elucidate the active compounds, mechanisms of action, and broader applications of this extract in combating antibiotic-resistant bacterial infections.

Low-dose and ultra-low-dose estradiol and dydrogesterone in postmenopause: an analysis by body mass index

Objective Oral, low-dose and ultra-low-dose continuous combined 17β-estradiol (E) plus dydrogesterone (D) reduce vasomotor symptoms (VMS) in postmenopausal women. Methods Two phase 3, double-blind studies were included. In the European study, postmenopausal women were randomized 2:1:2 to receive E0.5 mg/D2.5 mg (ultra-low dose), E1 mg/D5 mg (low dose) or placebo for 13 weeks. In the Chinese study, women were randomized 1:1 to receive E0.5 mg/D2.5 mg or placebo for 12 weeks. Post-hoc endpoints assessed in body mass index (BMI) subgroups (<25 kg/m2; ≥25 kg/m2) included number of hot flushes and moderate-to-severe hot flushes per day, and the proportion of women with amenorrhea. Results A total of 640 women were included. At the end of treatment, the mean (95% confidence interval) numbers of daily hot flushes were significantly lower (p ≤ 0.05) for all treatment groups versus placebo, with E0.5 mg/D2.5 mg (BMI < 25 kg/m2: 2.5 [1.9, 3.1]; BMI ≥ 25 kg/m2: 3.2 [2.5, 3.8]) and E1 mg/D5 mg versus placebo (BMI < 25 kg/m2: 2.7 [1.2, 4.2]; BMI ≥ 25 kg/m2: 2.3 [1.1, 3.5]) than with placebo (BMI < 25 kg/m2: 4.4 [3.8, 50]; BMI ≥ 25 kg/m2: 4.2 [3.6, 4.9]). A similar pattern was seen for moderate-to-severe hot flushes. The amenorrhea rate was high (79–98%) across both studies and BMI subgroups. Conclusion Oral, ultra-low-dose continuous combined E0.5 mg/D2.5 mg and low-dose continuous combined E1 mg/D5 mg alleviated postmenopausal VMS compared with placebo, irrespective of BMI.

Enhanced behavioral impact of optimized bupropion-encapsulated bilosomes over traditional niosomes treating depression.

Bupropion (Bpn), an FDA-approved NDRI (norepinephrine-dopamine reuptake inhibitor), poses risks of seizures and liver failure due to its stimulant properties, necessitating the development of alternative formulations. This research aims to develop a Bpn nanoformulation within bilosomal vesicles to enhance therapeutic efficacy at lower doses, using three bile salts, span 20 surfactants, and cholesterol via thin-film hydration. Optimization of bilosomal stability is achieved by trialing various ingredient concentrations, identifying a surfactant-to-cholesterol-to-bile salt ratio of 1.5:1:0.17µM, with sodium cholate (B.SCF) yielding the most stable system. Bpn encapsulated in the optimized bilosomal vesicle (Bpn@B.SC F) demonstrated high encapsulation efficiency of 78.142 ± 11.07% and drug-retaining capacity compared to the niosomal system. The in vitro and in vivo toxicity profile of the product is superior to the niosomal system and shows negligible toxicity with a viability rate of not less than 95%, with a sustained release profile in artificial cerebrospinal fluid (ACSF). In vivo, behavioral analysis on zebrafish revealed that Bpn@B.SC F treatment more effectively improved depressive behavior compared to free Bpn and other treatments, evidenced by increased exploration rates and reduced irregular movements, as shown through statistical and trajectory data. Hence, it is concluded that the bilosomal structure, compared to the niosomal system, is a better carrier of drugs to achieve brain delivery and improve mood.

Gamma ray irradiation on Swiss cheese estates (Monstera adansonii): growth, development, and variation

Purpose Swiss Cheese (Monstera adansonii) is an ornamental plant valued for its exotic leaves with openings and for the variety of colors. The technique of controlled exposure to gamma radiation was investigated to induce variegation (color change) in the leaves of this plant. Materials and methods Monstera adansonii cuttings were irradiated with different doses of radiation with 60Co gamma rays (0, 1, 5, 10, 15, and 20 Gy) and evaluated for size, color, health, and growth. Results Cuttings irradiated with 1 and 5 Gy exhibited temporary variegation in leaf color, but did not maintain these characteristics over time. Cuttings with higher doses of radiation (10, 15, and 20 Gy) did not survive well and showed a reduction in growth, number of leaves, health, and sprouting rate. Conclusions This research concludes that gamma radiation can affect the development of cuttings and shows the potential to induce variegation at lower doses, but more studies and prolonged observation are needed to determine whether this technique can produce variegation in a consistent and lasting way in M. adansonii. Therefore, although promising initial results have been observed, it is premature to state that gamma radiation is an effective method for inducing variegation in this plant.

Identification of Fusarium Wilt Disease Causal Agents in Pistachio Fields and Determination of Efficacy of Some Fungicides Controlling of of The Disease

Pistachio (Pistacia vera) propagation is commonly carried out by seedlings and new orchards are mostly set by in situ grafting of rootstocks. Pathogenic and molecular characterization of wilt and desiccation agents observed in nurseries and young orchards were carried out and the causal species were identified as Fusarium oxysporum and F. solani. In vitro inhibition of mycelial development and conidia germination were carried out with seven fungicides selected against the disease. The plant protection product containing Prothioconazole + Spiroxamine was found to be 100% effective in mycelial growth trials in F. oxysporum isolates from 20 mgL-1 and in F. solani from 100 mL-1 at all increasing doses. . The fungicide containing phosphoric acid was found to be 18.3%-33.3% effective on both species at 2.5 times the recommended dose. On conidial germination, Prothioconazole + Spiroxamine and Captan provided 100% inhibition even at the lowest doses in all isolates tested. The EC50 values of Prothioconazole + Spiroxamine, which was determined as the most effective chemical in mycelial development and conidial germination, were 3.67 ml and 3.72 ml in F. oxysporum isolates and 56.83 ml in F. solani, respectively.

Sida cordifolia Linn- An widely used herbs in the village of Falta, west Bengal, India: Pharmacological evaluation of antiepileptic activity of root extract of Sida cordifolia Linn.

As per the observation of the social work activitist it was found that the raw extract of the root of Sida cordifolia Linn. Are been used by some old people in the village of Falta Block of South 24 PGS district of West Bengal, India to treat epileptic attack on some villagers. The identified plant were collected and handed over the research scientists for the further study. The dried coarse powder of the root of Sida cordifolia Linn. Were soxheleted successively with petroleum ether (PESC), methanol (MESE), with boiled water (AESC) and the epileptic study was performed on the Albino mice using 100 and 300 mg/kg body weight of PESC, MESE and using clonazepam as standard using Maximum Electroshock induced seizure model and result depicted that PESC exhibited a significant antiepileptic effect at both low and high doses where as MESC exhibited the significant antiepileptic effect only at high dose. Hence, the petroleum ether extract may be chosen to be more effective than that of the methanol extract.

Mutual Interactions of Silymarin and Colon Microbiota in Healthy Young and Healthy Elder Subjects.

This multi-omic study investigates the bidirectional interactions between gut microbiota and silymarin metabolism, highlighting the differential effects across various age groups. Silymarin, the extract from Silybum marianum (milk thistle), is commonly used for its hepatoprotective effects. An in vitro fermentation colon model was used with microbiota from 20 stool samples obtained from healthy donors divided into two age groups. A combination of three analytical advanced techniques, namely proton nuclear magnetic resonance (1H NMR), next-generation sequencing (NGS), and liquid chromatography-mass spectrometry (LC-MS) was used to determine silymarin microbial metabolites over 24h, overall metabolome, and microbiota composition. Silymarin at a low diet-relevant dose of 50µgmL-1 significantly altered gut microbiota metabolism, reducing short-chain fatty acid (acetate, butyrate, propionate) production, glucose utilization, and increasing alpha-diversity. Notably, the study reveals age-related differences in silymarin catabolism. Healthy elderly donors (70-80 years) exhibited a significant increase in a specific catabolite associated with Oscillibacter sp., whereas healthy young donors (12-45 years) showed a faster breakdown of silymarin components, particularly isosilybin B, which is associated with higher abundance of Faecalibacterium and Erysipelotrichaceae UCG-003. This study provides insights into microbiome functionality in metabolizing dietary flavonolignans, highlighting implications for age-specific nutritional strategies, and advancing our understanding of dietary (poly)phenol metabolism.

Microplastic and the Enteric Nervous System: Effect of PET Microparticles on Selected Neurotransmitters and Cytokines in the Porcine Ileum

Microplastic is an environmental hazard to which both animals and humans are exposed. Current reports show that it can cause inflammation, including in the gastrointestinal tract. To examine the impact on the ileum, 15 eight-week-old gilts (five individuals/group) were exposed to PET microplastics (7.6 µm–416.9 µm) at a dose of 0.1 g/day or 1 g/day for 28 days. The collected ileum fragments were investigated for the cytokine concentrations (IL-1β, IL-6, IL-8, IL-10, and TNF-α; ELISA test), neuron populations (cocaine and amphetamine-regulated transcript, galanin, neuronal nitric oxide synthase, substance P, vesicular acetylcholine transporter, and vasoactive intestinal peptide; immunofluorescence staining), and morphometric parameters (histological analysis). Under the influence of MP-PET, there was a reduction in the populations of CART- and GAL-positive neurons in the submucosal plexuses and of nNOS-, VAChT-, and VIP-positive neurons in all the plexuses. In contrast, there was an increase in GAL-positive neurons in the myenteric plexus and SP-positive neurons in all the plexuses. The concentrations of IL-1β, IL-6, IL-8, IL-10, and TNF-α did not undergo statistically significant changes under the influence of the low or high dose of MP-PET. The changes in the histological structure exclusively concerned the thinning of the mucosa and the muscularis externa. The results support the thesis that MP-PET is not neutral to the ileal cells.

Determination of mutagenic effectiveness and efficiency of gamma rays and EMS in Coriander

Coriander is a dual purpose vegetable used as leaf as well as a spice, along with medicinal properties. Owing to its compound umbel and difficulty in crossing programme, mutation breeding is the available source to create variability. Mutagenesis is a well-recognized tool to expand genetic variability. The present investigation involves mutagenesis in coriander cv. Sindhu with physical (gamma rays) and chemical mutagens (EMS) and their combinations. The mutation frequency, mutagenic effectiveness and mutagenic efficiency were calculated for the gamma rays, EMS and their combination doses. In gamma rays, a drop in mutagenic effectiveness was observed at 10Kr followed by increase with higher concentration. Mutagenic effectiveness due to gamma rays, ranged from 6.5 to 8.51 due to EMS ranged from 42.09 to 49.55 and due to combination treatments ranged from 12.17 to 18.80 (5kr+0.2% EMS) in coriander variety, Sindhu. The mutagenic efficiency based on survival ranged from 1.78 to 4.0, injury ranged from 3.83 to 8.2, sterility ranged from 2.37 to 5.18 indicating differential response to different mutagens. The combination of gamma rays and EMS at lower and moderate doses expressed its worth to create higher mutation frequency by manifesting higher efficiency than the individual mutagens single-handed.