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Climbing fibers, connecting the inferior olive and Purkinje cells, form the nervous system's strongest neural connection. These fibers activate after critical events like motor errors or anticipation of rewards, leading to bursts of excitatory postsynaptic potentials (EPSPs) in Purkinje cells. The number of EPSPs is a crucial variable when the brain is learning a new motor skill. Yet, we do not know what determines the number of EPSPs. Here, we measured the effect of nucleo-olivary stimulation on periorbital elicited climbing fiber responses through in-vivo intracellular Purkinje cell recordings in decerebrated ferrets. The results show that while nucleo-olivary stimulation decreased the probability of a response occurring at all, it did not reduce the number of EPSPs. The results suggest that nucleo-olivary stimulation does not influence the number of EPSPs in climbing fiber bursts. [ABSTRACT FROM AUTHOR]

Aging is a multifaceted and progressive physiological change of the organism categorized by the accumulation of deteriorating processes, which ultimately compromise the biological functions. The objective of this study was to investigate the anti-aging potential of berberine (BBR) in D-galactose (D-Gal) induced aging in rat models. In this study, male Wistar rats were divided into four groups: The control group was given only vehicle, the BBR group was treated with berberine orally, the D-Gal group was treated with D-galactose subcutaneously and the BBR + D-Gal group was treated with D-galactose and berberine simultaneously. D-galactose exposure elevated the pro-oxidants such as malondialdehyde (MDA) level, protein carbonyl and advanced oxidation protein products (AOPP) in the brain. It decreased the anti-oxidants such as reduced glutathione (GSH) and ferric reducing antioxidant potential (FRAP) in the brain. D-galactose treatment also reduced the mitochondrial complexes (I, II, III and IV) activities and elevated the inflammatory markers such as interleukine-6 (IL-6), tumor necrosis factor- α (TNF-α) and C-reactive protein (CRP). The mRNA expressions of IL-6 and TNF-α in the brain were upregulated following D-galactose exposure. Berberine co-treatment in D-galactose induced aging rat model prevented the alteration of pro-oxidant and anti-oxidant in the brain. Berberine treatment restored the mitochondrial complex activities in the brain and also normalized the inflammatory markers. Based on these findings we conclude that berberine treatment has the potential to mitigate brain aging in rats via stabilizing the redox equilibrium and neuroinflammation. [ABSTRACT FROM AUTHOR]

Polycystic ovarian syndrome (PCOS) is a hormone disorder common among reproductive-aged women. This is associated with the symptoms like an irregular menstrual cycle, excess androgens, and polycystic ovary. Interestingly, vitamin E acts like the hormone progesterone and improves insulin sensitivity in PCOS. The study aims to evaluate the therapeutic effect of vitamin E in combination with combined oral contraceptive (COC) against PCOS by in silico and in vivo methods. The therapeutic effect of vitamin E (25 and 50mg/kg) in combination with COC (0.4mg/kg) was screened by the in silico method using Auto dock vina 4.2.6. Additionally, in vivo studies with a letrozole-induced PCOS model were performed in 30 female SD rats (n = 6 in each group) for 8 weeks with different doses of vitamin E. Furthermore, histopathological features and the insulin receptor (INSR) gene were scrutinized. An in silico study showed that drospirenone and vitamin E have an excellent affinity to bind to INSR and have higher binding energy (− 8.5 kcal/mol and − 8.7 kcal/mol, respectively). In vivo results showed a significant reduction in elevated testosterone levels compared to that of the PCOS group; follicle-stimulating hormone (FSH) and insulin levels also showed significant changes and reversed anti-oxidant levels in a dose-dependent manner. Ovarian histopathological changes were observed in different follicle counts in addition to the INSR gene, which showed changes in densitometry values. Supplementation of vitamin E combined with COC could be effective against PCOS, and clinical studies must be carried out further. [ABSTRACT FROM AUTHOR]

The purpose of this study was to validate an electronic portal imaging device (EPID) based 3-dimensional (3D) dosimetry system for the commissioning of volumetric modulated arc therapy (VMAT) delivery for flattening filter (FF) and flattening filter free (FFF) modalities based on test suites developed according to American Association of Physicists in Medicine Task Group 119 (AAPM TG 119) and pre-treatment patient specific quality assurance (PSQA).With ionisation chamber, multiple-point measurement in various planes becomes extremely difficult and time-consuming, necessitating repeated exposure of the plan. The average agreement between measured and planned doses for TG plans is recommended to be within 3%, and both the ionisation chamber and PerFRACTION™ measurement were well within this prescribed limit. Both point dose differences with the planned dose and gamma passing rates are comparable with TG reported multi-institution results. From our study, we found that no significant differences were found between FF and FFF beams for measurements using PerFRACTION™ and ion chamber. Overall, PerFRACTION™ produces acceptable results to be used for commissioning and validating VMAT and for performing PSQA. The findings support the feasibility of integrating PerFRACTION™ into routine quality assurance procedures for VMAT delivery. Further multi-institutional studies are recommended to establish global baseline values and enhance the understanding of PerFRACTION™'s capabilities in diverse clinical settings. [ABSTRACT FROM AUTHOR]

Purpose: Products formulated for intramammary (IMM) infusion are intended for the delivery of therapeutic moieties directly into the udder through the teat canal to maximize drug exposure at the targeted clinical site, the mammary gland, with little to no systemic drug exposure. Currently, to our knowledge, there has been no in-vitro matrix system available to differentiate between IMM formulations. Our goal is to develop A custom tailored in-vitro "Matrix of Chemistry, Manufacturing and Control" (MoCMC) System to be a promising future tool for identifying inequivalent IMM formulations. MoCMC can detect inter and intra batch variabilities, thereby identifying potential generics versus brand product similarities or differences with a single numeric value and a specific & distinctive fingerprint. Methods: The FDA-approved IMM formulation, SPECTRAMASTⓇ LC, was selected as the reference product for the MoCMC. Twelve in-house test formulations containing ceftiofur hydrochloride were formulated and characterized. The MoCMC was developed to include six input parameters and three output parameters. The MoCMC system was used to evaluate and compare SPECTRAMASTⓇ LC with its in-house formulations. Results: Based on the MoCMC generated parameters, the distinctive fingerprints of MoCMC for each IMM formulations, and the statistical analyses of MCI and PPI values, in-house formulations, F-01 and F-02 showed consistency while the rest of in-house formulations (F-03-F-12) were significantly different as compared to SPECTRAMASTⓇ LC. Conclusion: This research showed that the MoCMC approach can be used as a tool for intra batch variabilities, generics versus brand products comparisons, post-approval formulations changes, manufacturing changes, and formulation variabilities. [ABSTRACT FROM AUTHOR]

Despite considerable advancement of first choice treatment (pharmacological, physical therapy, etc.) over many decades, neurological disorders still represent a major portion of the worldwide disease burden. Particularly concerning, the trend is that this scenario will worsen given an ever expanding and aging population. The many different methods of brain stimulation (electrical, magnetic, etc.) are, on the other hand, one of the most promising alternatives to mitigate the suffering of patients and families when conventional treatment fall short of delivering efficacious treatment. With applications in virtually all neurological conditions, neurostimulation has seen considerable success in providing relief of symptoms. On the other hand, a large variability of therapeutic outcomes has also been observed, particularly in the usage of noninvasive brain stimulation (NIBS) modalities. Borrowing inspiration and concepts from its pharmacological counterpart and empowered by unprecedented neurotechnological advancement, the neurostimulation field has seen in recent years a widespread of methods aimed at the personalization of its parameters, based on biomarkers of the individuals being treated. The rationale is that, by taking into account important factors influencing the outcome, personalized stimulation can yield a much-improved therapy. Here, we review the literature to delineate the state-of-the-art of personalized stimulation, while also considering the important aspects of the type of informing parameter (anatomy, function, hybrid), invasiveness, and level of development (pre-clinical experimentation versus clinical trials). Moreover, by reviewing relevant literature on closed loop neuroengineering solutions in general and on activity dependent stimulation method in particular, we put forward the idea that improved personalization may be achieved when the method is able to track in real time brain dynamics and adjust its stimulation parameters accordingly. We conclude that such approaches have great potential of promoting the recovery of lost functions and enhance the quality of life for patients. [ABSTRACT FROM AUTHOR]

Cervical cancer is one of the most prevalent forms of cancer, with a lengthy latent period and a gradual onset phase. Conventional techniques are found to be severely lacking in real time detection of disease progression which can greatly enhance the cure rate. Due to their high sensitivity and specificity, optical techniques are emerging as reliable tools, particularly in case of cancer. It has been seen that biochemical changes are better highlighted through intrinsic fluorescence devoid of interference from absorption and scattering. Its effectiveness in in‐vivo conditions is affected by the fact that the intrinsic spectral signatures vary from patient to patient, as well as in different population groups. Here, we overcome this limitation by collectively enumerating the subtle changes in the spectral profiles and correlations through an information theory based entropic approach, which significantly amplifies the minute spectral variations. In conjunction with artificial intelligence (AI)/machine learning (ML) tools, it yields high specificity and sensitivity with a small dataset from patients in clinical conditions, without artificial augmentation. We have used an in‐house developed handheld probe (i‐HHP) for extracting intrinsic fluorescence spectra of human cervix from 110 different subjects drawn from diverse population groups. The average classification accuracy of the proposed methodology using 10‐fold cross validation is 93.17%. A combination of polarised fluorescence spectra from i‐HHP and the proposed classifier is proven to be minimally invasive with the ability to diagnose patients in real time. This paves the way for effective use of relatively smaller sized sensitive fluorescence data with advanced AI/ML tools for early cervical cancer detection in clinics. [ABSTRACT FROM AUTHOR]

In this study, a series of nine novel heterocyclic compounds were synthesized through a concise three-step reaction process. The synthesis involved Knoevenagel condensation at the 5th position of the 2,4-thiazolidinedione or rhodanine ring-system. Comprehensive physicochemical and spectral analyses, including FTIR, Mass, 1H NMR and 13C NMR, were performed to characterize the synthesized compounds. The synthesized derivatives were subjected to evaluation for their potential in various therapeutic domains. In-vivo anti-diabetic activity was assessed diabetes induced wistar rats, anti-inflammatory effects were gauged using the carrageenan and formalin induced rat paw edema model. Additionally, the in-vitro PPAR-γ modulatory activity, glucose uptake by using Saccharomyces cerevisiae and rat hemidiaphragm and cyclooxygenase inhibitory activity along with scavenge free radicals was tested by FRAP and DPPH method. According to the potential binding patterns of the most potent anti-diabetic compounds, namely 7a and 13a with the active sites of target PPAR-γ (PDB ID: 5U5L), was obtained through molecular docking using Schrodinger’s Glide model. Among the tested compounds, the compound 13a demonstrated significant antidiabetic activity with reduction in blood glucose levels (108.5 ± 2.171 mg/dL), comparable to the effect of pioglitazone (101.66 ± 0.95 mg/dL), similarly anti-inflammatory activity at fourth hour paw volume 93.6% and thickness at 3.99 ± 0.076 mm, respectively closer to that of standard drug diclofenac sodium (91.2% and 4.7 ± 0.057 mm) in carrageenan-induced paw edema in rat. The compound 13a displayed promising COX-2 inhibitory activity (IC50 = 7.82 μM) and DPPH antioxidant activity showcasing its multifaceted therapeutic potential. This study not only presents multi-targeting approach and highlights the significant potential compounds as a lead molecule for further therapeutic development.

This study presents a new in-vivo microwave imaging method to determine the blood glucose levels of mice directly from their tail using a thermo-elastic optical indicator microscope (TEOIM). By measuring the microwave near-field distribution intensity around the tail, the changing trend of the glucose level can be detected non-invasively when the mouse tail is exposed to 7 GHz microwave irradiation. The microwave electric field distribution was visualized by the metasurface-based optical indicator, showing that the average intensity values are proportional to the blood glucose levels. The clinical accuracy of TEOIM glucose monitoring systems was evaluated using the Clarke error grid (CEG) analysis method, where 100% of the measurement points were in the A + B zone of the CEG. Based on the experimental results, the TEOIM can adequately detect the blood glucose concentration in the 170-500 mg/dL range. The testing results achieve a mean absolute relative difference (MARD) of 7.05% for the measurement and a root mean squared error (RMSE) of 24.85 mg/dL. The potential improvement methods of the imaging system for non-invasive glucose measurement were discussed, emphasizing future research plans to enhance accuracy and validation, which may positively impact healthcare and diabetes screening. This method provides a novel approach for the non-invasive sensing of blood glucose concentrations in-vivo using a CCD sensor.

Purpose: The objective of the present investigation was to establish a molecular association of different proteases as cancer targets with the indinavir and how the physicochemical characteristics of the indinavir sulfate microsphere vary with different process variables was systemically established. Methods: Molecular interactions with indinavir were identified and established by molecular simulation docking studies. Indinavir sulfate-loaded microspheres were prepared by the oil-in-oil emulsion solvent evaporation technique. Results: Results indicated that indinavir could interact with all four proteases at the active binding site of receptors. Indinavir was found to show significantly higher interaction with Matrix Metalloproteases, Aspartate Proteases, and Cysteine Proteases with a binding energy of -8.80, -8.19, and -6.87, respectively, as compared to their native ligand. However, serine proteases exhibit less but significant interaction with a binding energy of -5.92 than the native ligand. The microspheres exhibited 72%-93% of entrapment and prolonged drug release (DR), up to 9 h. The drug-loaded microspheres showed invariable character by the Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermographs and revealed no drug-polymer interactions. The decrease in the drug's crystallinity was observed in X-ray diffraction (XRD). The scanning electron microscope (SEM) study revealed the spherical and porous nature of microspheres. Conclusion: Indinavir could act as a potential inhibitor of different proteases associated with tumor growth initiation, progression, and metastasis, and microspheres with sustained DR could be utilized to deliver an anticancer drug in a more targeted way as an emerging cancer microsphere technology. [ABSTRACT FROM AUTHOR]

The in-situ mechanical characterization of elastomers is not highly regarded due to the existence of a well-established set of sample-based standard tests for research and industry. However, there are certain situations or materials, like biological soft tissue, where an in-situ approach is necessary due to the impossibility of sampling from a living body. We have developed a dynamic mechanical analysis (DMA)-like device to approach in-vivo and in-situ multidimensional stress-strain properties of human plantar soft tissues. This work elucidates the operational mechanism of the novel measurement, with the definition of a new set of moduli, test standardization and protocol. Exploratory results of a volunteer's living plantar, silica rubber samples are presented with well preciseness and consistence as expected.

Introduction: Hyperuricemia is a metabolic disease characterized by an increase in serum uric acid levels. Hyperuricemia can be controlled by low purine diet or drugs like allopurinol and febuxostat; however, the incidence of adverse effects to these drugs, especially on chronic use, is a major clinical problem. Swertia chirayita; a herb from Gentianaceace family, was selected to observe it’s in vivo uric acid lowering effect in white Albino Wistar rats in whom hyperuricemia was induced through potassium oxonate. Febuxostat was used as a standard. Aims and Objectives: To observe the in vivo effect of different doses of Swertia chirayita extract (SCE) on uric acid levels and to compare its effect with the allopathic medicine febuxostat. Place and Duration of study: A randomized controlled study was held at University of Health Sciences Lahore between June- August 2017. Material and Methods: Forty-eight healthy adult Albino Wistar rats were randomly divided into six groups. Group I and II served as negative and positive controls respectively. Hyperuricemia was induced by injecting KO solution (01ml) intraperitoneally on 1st, 3rd and 7th day of study. Group III received febuxostat 5 mg/kg through oral gavage. Group IV, V and VI were experimental groups, treated with 100, 200 and 400 mg/kg doses of Swertia Chirayita extract respectively through oral route, 02 hours after induction by KO once daily for 07 days. Blood samples were collected to record serum uric acid levels on day zero, first, third and seventh days. (SPSS)version 20 was used for data entry and analysis, pvalue ? 0.05 was given statistical importance. Results: In all experimental groups (IV, V, VI), serum uric acid levels were significantly reduced by Swertia chirayita extract (SCE) (p ? 0.001) as compared to hyperuricemic rats (group II). SCE showed dose dependent SUA suppression. Results of both febuxostat and SCE showed that average SUA levels of these groups were markedly less than hyperuricemic rats (Group II) (p < 0.001) Conclusion: In the light of its hypouricemic activity; we conclude that in the future, Swertia chirayita has the potential for newer therapeutic applications in this regard.

This paper presents a novel approach to the design of a brain implantable antenna tailored for brain-machine interface (BMI) technology. The design is based on a U-shaped unit-cell metamaterial (MTM), introducing innovative features to enhance performance and address specific challenges associated with BMI applications. The motivation behind the use of the unit-cell structure is to elongate the electric path within the antenna patch, diverging from a reliance on the electrical properties of the MTM. Consequently, the unit cell is connected to an inset-fed transmission line and shorted to the ground. This configuration serves the dual purpose of reducing the size of the antenna and enabling resonance at the 2.442 GHz band within a seven-layer brain phantom. The antenna is designed using a FR-4 substrate (εr = 4.3 and tan δ = 0.025) of 1.5 mm thickness, and it is coated with a biocompatible polyamide material (εr = 4.3 and tan δ = 0.004) of 0.05 mm thickness. The proposed antenna achieves a compact dimension of 20 × 20 × 1.6 mm3 (0.338 × 0.338 × 0.027 λg3) and demonstrates a high bandwidth of 974 MHz with its gain of −14.6 dBi in the 2.442 GHz band. It also exhibits a matched impedance of 49.41-j1.32 Ω in the implantable condition, corresponding to a 50 Ω source impedance. In comparison to a selection of relevant research works, the proposed antenna has a low specific absorption rate (SAR) of 218 W/kg and 68 W/kg at 1g and 10g brain tissue standards, respectively. An antenna prototype has been fabricated and measured for return loss in both free space and in-vivo conditions using sheep's brain. The measurement results are found to be in close agreement with the simulation results for both conditions, showing the practical applicability of the proposed antenna for BMI applications.

Despite considerable advancement of first choice treatment (pharmacological, physical therapy, etc.) over many decades, neurological disorders still represent a major portion of the worldwide disease burden. Particularly concerning, the trend is that this scenario will worsen given an ever expanding and aging population. The many different methods of brain stimulation (electrical, magnetic, etc.) are, on the other hand, one of the most promising alternatives to mitigate the suffering of patients and families when conventional treatment fall short of delivering efficacious treatment. With applications in virtually all neurological conditions, neurostimulation has seen considerable success in providing relief of symptoms. On the other hand, a large variability of therapeutic outcomes has also been observed, particularly in the usage of non-invasive brain stimulation (NIBS) modalities. Borrowing inspiration and concepts from its pharmacological counterpart and empowered by unprecedented neurotechnological advancement, the neurostimulation field has seen in recent years a widespread of methods aimed at the personalization of its parameters, based on biomarkers of the individuals being treated. The rationale is that, by taking into account important factors influencing the outcome, personalized stimulation can yield a much-improved therapy. Here, we review the literature to delineate the state-of-the-art of personalized stimulation, while also considering the important aspects of the type of informing parameter (anatomy, function, hybrid), invasiveness, and level of development (pre-clinical experimentation versus clinical trials). Moreover, by reviewing relevant literature on closed loop neuroengineering solutions in general and on activity dependent stimulation method in particular, we put forward the idea that improved personalization may be achieved when the method is able to track in real time brain dynamics and adjust its stimulation parameters accordingly. We conclude that such approaches have great potential of promoting the recovery of lost functions and enhance the quality of life for patients.

Coelogyne suaveolens has been used as a traditional medicine for many years, and its potential as a natural source of antibacterial agents is of great interest. This investigation aimed to identify the bioactive compounds in the plant extract and assess their antibacterial properties. To achieve this, we identified the bioactive compounds using Gas chromatography mass spectrometry (GCMS) analysis on the extract's ethyl acetate fraction and used the disc diffusion method to determine the antibacterial effect. Additionally, molecular docking were performed to predict the binding affinities of selected phytochemicals against specific proteins in order to identify the root cause of bacterial inhibition. Our results revealed that the extract exhibited significant antibacterial activity against Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae, which are common and problematic pathogens. Furthermore, molecular docking studies identified eight best-selected compounds, of which {androstan-17-one, oxime, (5.alpha.)-}, diethofencarb, tetraconazole, {3,6-dimethyl-2,3,3a,4,5,7a-hexahydrobenzofuran}, and geranyl acetate showed a significant binding affinity with best binding interaction with the target enzymes. This suggests that binding to these specific proteins might lead to the mechanism of action of the evaluated antibacterial action. In conclusion, the present study contributes to the growing body of knowledge on natural antimicrobial agents and could have significant implications for the development of new and effective antibacterial agents.

The evidence for the use of Augmented Reality (AR) in treating specific phobias has been growing. However, issues of accessibility persist, especially in developing countries. The current study examined a novel, but relatively simple therapist guided smartphone-based AR Exposure Treatment (ARET) of spider phobia. Participants who reported symptoms of Arachnophobia were randomized into one of three comparison groups: ARET (n = 20), traditional in vivo exposure therapy (IVET; n = 18) and a waitlist control group (n = 17). Behavioral approach, subjective symptom measures, and galvanic skin response were assessed pre- and post-treatment. The study was concluded with a one-month follow up assessment. Results indicated that both treatment groups showed statistically significant and clinically meaningful improvements in behavioral approach at post-test that were maintained at 1 month follow- up, compared to the wait-listed group. Moreover, the treatment groups demonstrated significant improvements in subjective symptom report at 1-month follow up. Given its utility and potential accessibility, our findings suggest that future AR evaluation research could be conducted in therapy settings with minimal resources.

This study aims to evaluate effect of Colocasia esculenta and Zingiber officinale combined extract (CEZO) in osteoarthritis rats. Twenty-four Wistar rats were split into normal group, positive group, negative group, and CEZO group on 29th to 43rd day (n = 6). All rats were injected with Na-iodoacetate intraarticularly on first day, unless for the normal group, and then observing the diameter of knee edema until the 28th day (OA rats). On the 43rd day, rats were euthanasia for measurements of hematology, spleen weight, and inflammatory mediators of nitric oxide, matrix metalloproteinase 9, Interleukin-6, and tumor necrosis factor-α using ELISA kit. Our experiments showed that CEZO 90 mg/kgBW was able to decrease knee edema, leukocytes, lymphocytes, spleen enlargement, the concentration of mediators inflammatory NO, TNF-α, IL-6, and protect cartilage degradation by decreased MMP-9 significantly in OA rats. Conclusion of the research is the CEZO 90 mg/kgBW supplementation has potential to be used in osteoarthritis. [ABSTRACT FROM AUTHOR]

The development of effective antiepileptic drugs (AEDs) is crucial in the management of epilepsy, a chronic neurological disorder characterized by recurrent seizures. In order to identify potential AEDs, researchers employ a range of screening models that encompass both in-vitro and in-vivo approaches. These models provide valuable insights into the pharmacological properties and mechanisms of action of candidate compounds, aiding in the selection and optimization of drug candidates for further development. In-vitro screening models involve conducting experiments on isolated cells or tissues in controlled laboratory conditions. They allow researchers to examine the effects of AEDs on specific molecular targets involved in epileptogenesis, such as ion channels or neurotransmitter receptors. In-vitro models offer advantages such as cost-effectiveness, high throughput capacity, and the ability to study drug interactions with isolated components of the nervous system. Furthermore, they facilitate mechanistic investigations that elucidate the underlying pathways through which AEDs exert their antiepileptic effects. Hence, this review was focused for the various methods indicating the In-vitro and In-vivo pharmacological screening models for antiepileptic drugs. [ABSTRACT FROM AUTHOR]

Drinking water in areas with a high prevalence of chronic kidney disease of unknown aetiology (CKDu) in Sri Lanka, is known to have high concentrations of fluoride and hardness. The present study evaluated the individual and combined effects of water hardness and fluoride on potential nephrotoxicity, using Wistar rats as an animal model. Thirty-five Wistar rats were randomly assigned into five groups (n=7). Test groups F, H, RL, and RH were given de-ionized water containing 1.5 mg/L fluoride, 200 mg/L hardness, 1.5:200 mg/L fluoride: hardness, and 5:800 mg/L fluoride: hardness respectively, while control group C was given de-ionized water. Body weight and daily water consumption were measured. Serum creatinine, urine creatinine, and urinary biomarker KIM-1 were analyzed. Histopathological changes in the kidneys were observed. There were no significant differences in body weights (p>0.05) while daily water consumption was reduced significantly in the test groups RL and RH (p<0.05). A significant increment in serum creatinine in the RL and RH groups (p<0.05), and a significant reduction in urine creatinine in the F, H, RL and RH groups (p<0.05), were recorded compared to the control. However, the highest magnitude of the effect on serum creatinine and urine creatinine was recorded in the RL group. Significant increment in KIM-1 levels were recorded in the RH group (p<0.05) while the RH group indicated a more rapid increment from the 28th day. When considering histopathology, renal tubular changes were observed in the test groups. The individual and combined effects of water hardness and fluoride may contribute to the aetiology of CKDu in Sri Lanka. [ABSTRACT FROM AUTHOR]

• Prolamin hydrolysate of C. lanatus rich in amino acids serve as good source of nutrition. • The hydrolysate of the prolamin from C. lanatus exhibited remarkable antibacterial action against Gram-negative infections. • The prolamin hyrolysate of C. lanatus shows potential role in eliminating P. aeruginosa in the animal model. In recent years, the exploration of novel antibiotic agents from natural sources has gained significant attention in today's research due to a rapid increase in resistance to the existent synthetic drugs. The antimicrobial activity of prolamin hydrolysate of Citrullus lanatus (CLPH) was carried out using two different in-vitro antimicrobial methods (viable cell count method and broth-based turbidometric assay) against both Gram-positive and Gram-negative bacteria. The in-vivo antibacterial effect of CLPH against Pseudomonas aeruginosa was evaluated in detail using the animal model. The total protein content and amino acid compositions of CLPH was also determined. CLPH exhibited high efficacy towards Gram-negative bacteria and inhibited the growth of P. aeruginosa (37±3.1 µg/ml). The CLPH shows a potential role in eliminating P. aeruginosa in the animal model. Among all identified amino acids, arginine content in CLPH was found to be 189.4 mg/100 g. P. aeruginosa is a Gram-negative bacterium, which develops multi-drug resistance and enhances antibiotic resistance rate. Therefore, this outcome may have significant importance in the development of novel antibiotics from the food source for the treatment of bacterial infections. [ABSTRACT FROM AUTHOR]

An attempt was taken to control initial growth of pomegranate plantlets by application of plant extracts as foliar spray under field circumstances. A modified preparation of 'Dashparni extract', was developed using leaf extracts of Vitex negundo, Aristolochia sp., Carica papaya, Tinospora cordifolia, Annona squamosa, Pongamia pinnata, Ricinus communis, Nerium indicum, Calotropis procera, Green chilli paste, Garlic paste applied to regulate growth and development of pomegranate saplings. The Dashaparni extract proved to be more effective than all other tests conducted as well as control (distilled water spray). The extract boosted overall growth of plantlets and disease resistance. [ABSTRACT FROM AUTHOR]

The ideal biomaterials substitute for bone repair should possess the following characteristics: provide osteogenic, osteoinductive and osteoconductive properties; stimulate the neo-angiogenesis process; absence of antigenic, teratogenic or carcinogenic reactions; avoid the systemic toxicity complications; assure satisfactory support and stability from mechanical properties point of view; hydrophilic nature of the surface properties and good interface with human bone; good handling in clinical condition and ability to be easy sterilized; and able to be supplied in sufficient quantities with reduced costs. Despite years of effort, the perfect bone reconstruction material has not yet been developed; further effort is required to make this objective feasible. The aim of this article is to provide a contemporary and comprehensive overview of the grafting materials that can be applied for the treatment of bone defects by the clinicians from orthopedics surgery, neurosurgery and dentistry, discussing their properties, advantages and disadvantages, and illuminating present and future perspectives in the field of bone graft and biomaterials substitutes for bone repair, from clinical needs to advanced biomaterials research. [ABSTRACT FROM AUTHOR]

Chalcones in combination with heterocyclic moieties have been reported to exhibit diverse biological activities. The present study was aimed to synthesize novel chalcones bearing pyrazoline moiety and Michael adducts. All the synthesized compounds were characterized by various spectral techniques, and screened for their anti-inflammatory potential. Most of the synthesized compounds exhibited good to moderate activity. The results of the experiment were statistically processed using GraphPad Prism 9.0. The compounds were also docked to get an insight of the binding interaction pattern with the active site of the target protein, and the results were found to be in consonance with the experimental findings. In-silico ADMET prediction was carried out for the title compounds. The study concludes that the synthesized compounds exhibit potential in supressing inflammation, and therefore can be considered for designing more such compounds as anti-inflammatory agents. Also, since the synthesized title compounds are non-carboxylic analogs, they may be considered as non-ulcerogenic, safe and effective anti-inflammatory agents. [ABSTRACT FROM AUTHOR]

The development of carriers for drug delivery faces significant challenges from a therapeutic perspective. The present study presents an innovative nanocarrier based on combination of functionalized magnetic nanocomposite nano‐chitosan and cisplatin. Hydrophobic drugs such as cisplatin could be delivered using magnetic nanoparticles modified with biocompatible copolymers. This study aimed to determine the antitumor effects of free cisplatin enhancement in cervical cancer cells using cisplatin‐encapsulated Fe3O4@SiO2@N‐Chit‐FA. An additional layer of nanochitosan was coated on top of the magnetic nanocomposite to increase its stability in aqueous solutions. Biocompatibility and cytotoxicity of Fe3O4@SiO2@N‐Chit‐FA‐cis complex were evaluated against the cervical cancer animal model in C57BL6 mice. An external magnetic field was used to test the in‐vivo uptake and distribution of Fe3O4@SiO2 @N‐Chit‐FA‐cis in tumor cells. The results showed that the released drug would induce its effects on a specific target area when an external magnetic field was applied, and Fe3O4@SiO2@N‐Chit‐FA‐cis can suppress tumor growth more than cisplatin alone via induction of tumor necrosis. Overall, Fe3O4@SiO2@N‐Chit‐FA nanocomposites hold great potential for use in targeted nanomedicine to deliver bio‐functional molecules. [ABSTRACT FROM AUTHOR]

Currently, common optical techniques to measure tissue oxygen saturation (StO2) include time domain (TD), frequency domain (FD), and continuous wave (CW) near-infrared spectroscopy (NIRS). While TD- and FD-NIRS can provide absolute hemoglobin concentration, these systems are often complex and expensive. CW-NIRS, such as diffuse reflectance spectroscopy and spatially resolved spectroscopy (SRS), are simpler and more affordable, but they still require at least two source-detector separations. Here, we propose a single source-detector separation (SSDS) approach to measure StO2 using reflected intensities from three wavelengths. The accuracy of the SSDS-based StO2 measurement was verified using an optical simulation and an in-vivo experiment. Simulated spatially dependent reflectance was generated using the Virtual Tissue Simulator on a 1-layer model, which has StO2 ranging from 0% to 100%. SSDS calculation yielded an equivalent StO2 to the actual value (average error = 0.3% ± 0.5%). We then performed StO2 measurements on seven healthy volunteers in the prefrontal cortex during a simulated hypercapnia test using a CW-NIRS device. This device consists of a light source and two photodetectors, which are 30 mm and 40 mm away from the light source. The cerebral oxygen saturation was calculated using both the SRS approach, which uses the reflected intensities at both separations, and the SSDS approach, which employs the reflected intensities at either 30 mm or 40 mm separation. The SRS-based StO2 calculation was similar to the value calculated from the SSDS method (average difference = 5.0% ± 1.1%). This proposed method will help to advance the development of miniaturized technologies to monitor StO2 continuously.

Recently, developing bioactive and biocompatible materials based on Mg and Mg-alloys for implant applications has drawn attention among researchers owing to their suitable body degradability. Implementing Mg and its alloys reduces the risk of long-term incompatibility with tissues because of their close mechanical properties and no need for re-operation to remove the implant. Nevertheless, the degradation rate of the implant needs to be controlled because production of hydrogen gas and accumulation of its bubbles increases local pH around the implants. To confine the integrity of implants and the body, the corrosion concern in the body fluid requires to be addressed. Surface modification as one of the effective strategies can improve corrosion resistance. Besides, it creates a suitable surface for bone grafting and cell growth. The development of proper surface-coated implants needs appropriate techniques and approaches. Plasma electrolytic oxidation (PEO) coating can provide long-term protection by providing a ceramic layer and improving the implant's biocompatibility. Herein, a general review of in-vivo and in-vitro evaluation of PEO coatings on Mg and Mg-alloys has been carried out. Recent advances in surface modification on Mg and Mg-alloys have been discussed, however, the need for reliable laboratory models to predict in-vivo degradation is still valid.

A novel pyrazole condensed with chalcone and pyrazoline derivatives have been synthesized and evaluated against antiinflammatory activity using a standard method of acute carrageenan-induced rat paw edema in vivo. NJD1 would be the most potent compound (30.10 ± 0.02%) found to be inhibitory in rats and exhibiting activity similar to celecoxib as a reference standard. Molecular docking studies have been conducted on PDB: 1TD7, the 3D X-ray crystallographic structure of group I protein phospholipase A2 (PLA2), -5.609 kcal/mol is the binding affinity of the standard celecoxib. The synthesized derivatives NJD1 and NJD2 (-6.283, -6.057 kcal/mol) has exhibited greater binding affinity, respectively. [ABSTRACT FROM AUTHOR]

Aims : This study was designed to provide both ex-vivo and in-vivo methods for the extraction and expansion of spermatogonial stem cells (SSCs). Methods: For in-vivo experiments, azoospermic mouse model was performed with Busulfan. Isolation, culture, and characterization of neonate mouse SSC were also achieved. We performed an in-vivo injection of labeled SSCs to the testes with azoospermia. In ex-vivo experiments, extracted SSCs were seeded on the fabricated scaffold consisting of hyaluronic acid (HA) and decellularized testis tissues (DTT). Immunofluorescence staining with PLZF, TP1, and Tekt 1 was performed for SSCs differentiation and proliferation. Results: Several studies demonstrated efficient spermatogenic arrest in seminiferous tubules and proved the absence of spermatogenesis. Transplanted SSCs moved and settled in the basement covering the seminiferous tubules. Most of the cells were positive for Dil, after 4 weeks. An epithelium containing spermatogonia-like cells with Sertoli-like, and Leydig cells were evident in the seminiferous tubules of biopsies, and the IHC staining was significantly positive, 4 weeks after injection of SSCs. The results of the ex-vivo experiments showed positive staining for all markers, which was significantly enhanced in scaffolds of ex-vivo experiments compared with in-vitro seeded scaffolds. Conclusion: Ex-vivo SSC differentiation and proliferation using cell-seeded microfluidic testis scaffolds maybe effective for treatment of the azoospermia. [ABSTRACT FROM AUTHOR]

The ability of influenza viruses to incessantly mutate makes these viruses to circulate in the field continuously. Every year, economic losses are faced by poultry industry due to vaccine failure. The current study was designed to bridge the gap by using various bioinformatics tools. For B-cells, HA protein of study virus showed 85.45% epitopes conservancy with vaccine 4 (local vaccine) whereas 54.54%, 67.27% and 43.63% were found conserved in vaccines 3, 2 and 1 (imported vaccines) respectively. For NA protein of study virus, 87.03% epitopes were found conserved in vaccine 4 whereas in vaccines 3, 2 and 1, 18.14%, 50% and 37.03% were found conserved respectively. Slight different results were obtained for T-cells. For MHC-1, vaccine 2 showed highest conservancy of 70% with HA protein of our study virus whereas, vaccine 1 and 3 showed 50% and vaccine 4 showed 60% conservancy. In case of NA protein 90%, 54%, 45% and 36% epitopes were conserved in vaccines 4, 3, 2 and 1 respectively against MHC-1 molecules. For MHC-2, HA protein of our study virus, vaccine 2 and 4 showed 84% conservancy whereas vaccine 1 and 3 showed 53% conservancy. While for NA protein, 100%, 28%, 71%, and 57% epitopes were conserved in vaccines 4, 3, 2 and 1 against MHC-2 molecules. In-vivo trials also supported in-silico results. Groups vaccinated with vaccine 1 and 3 respectively, showed significant levels of morbidity and post-challenge virus shedding through buccal and cloacal swab as compared to vaccine 2 and 4 respectively. Our study shows that there is a need of continuous evaluation and upgradation of seed virus of H9N2 vaccines, for this purpose in-silico analysis is a reliable and efficient method.

In this present research, an attempt has been made to address the influence of drug-coformer stoichiometric ratio on cocrystal design and its impact on improvement of solubility and dissolution, as well as bioavailability of poorly soluble telmisartan. The chemistry behind cocrystallization and the optimization of drug-coformer molar ratio were explored by the molecular docking approach, and theoretical were implemented practically to solve the solubility as well as bioavailability related issues of telmisartan. A new multicomponent solid form, i.e., cocrystal, was fabricated using different molar ratios of telmisartan and maleic acid, and characterized by SEM, DSC and XRD studies. The molecular docking study suggested that specific molar ratios of drug-coformer can successfully cluster with each other and form a specific geometry with favourable energy conformation to form cocrystals. Synthesized telmisartan-maleic acid cocrystals showed remarkable improvement in solubility and dissolution of telmisartan by 9.08-fold and 3.11-fold, respectively. A SEM study revealed the formation of cocrystals of telmisartan when treated with maleic acid. DSC and XRD studies also confirmed the conversion of crystalline telmisartan into its cocrystal state upon treating with maleic acid. Preclinical investigation revealed significant improvement in the efficacy of optimized cocrystals in terms of plasma drug concentration, indicating enhanced bioavailability through improved solubility as well as dissolution of telmisartan cocrystals. The present research concluded that molecular docking is an important path in selecting an appropriate stoichiometric ratio of telmisartan: maleic acid to form cocrystals and improve the solubility, dissolution, and bioavailability of poorly soluble telmisartan. [ABSTRACT FROM AUTHOR]

The ability of unicompartmental knee arthroplasty (UKA) to restore native knee kinematics during activities of daily living remains unclear. The objectives of this prospective study were to identify changes in knee kinematics after medial UKA (mUKA) and to determine if mUKA restores native knee kinematics during activities of daily living. We hypothesized that kinematics are different between the mUKA knee and contralateral knee before surgery, that mUKA restores native knee kinematics, and that mUKA does not affect lateral compartment dynamic joint space. Nine participants performed walking, chair rise, stair ascent and stair descent within a biplane radiography system before and after mUKA. Bilateral knee kinematics were determined for each activity using a validated tracking process that matched subject-specific bones and implants to the biplane radiographs. Compared to contralateral knee, the pre-UKA knee was more adducted (p ≤ 0.019), and more laterally translated (p ≤ 0.008) during all four activities. Additionally, compared to contralateral knee, pre-UKA knee was less internally rotated (p ≤ 0.044) during chair rise and stair ascent. Lateral compartment dynamic joint space did not change during any activity from pre to post mUKA. Our results indicate that mUKA generally restores native kinematics during activities of daily living without altering lateral compartment dynamic joint space. [ABSTRACT FROM AUTHOR]

Objective: In this study, applicability of an in-vitro ELISA method, which reduces or eliminates the need for animal trials in establishing the efficacy of inactive Newcastle disease vaccines was investigated. Methods: For this purpose, the efficacy of nine (9) inactivated Newcastle disease vaccines and two non-Newcastle related vaccines (negative controls) were evaluated by in-vivo and in-vitro methods. As in-vivo tests, vaccines were applied to the Spesific Pathogen Free (SPF) chicks and antibody response was determined via hemagglutination inhibiton test. As in-vitro, antigen amount in vaccines were calculated with a sandwich ELISA test based on the determination of hemagglutinin and neuraminidase levels developed for inactive Newcastle vaccines. Relative potency values of vaccines were calculated by using the parallel line analysis method with Combistats statistical analysis software program by using optical density results obtained from ELISA test. Results: Hemagglutination inhibition test results were found to be between 23,3 and 26,1; immunization/challenge results ranged between 56 and 136 PD50 and ELISA test results were between 6,02 and 98,23 antigen units. A correlation was found between the ELISA test and in-vivo methods. Sensitivity and specificity were found to be %89, %100 respectively. Conclusion: In our study according to these results, we have demonstrated the ability of ELISA method to give similar results on the same samples, its compatibility with the standard procedure and its applicability under laboratory conditions. [ABSTRACT FROM AUTHOR]

Zingiber officinale rhizome and Centella asiatica leaves are extensively consumed as dietary supplements, and they are also reported for their antidiabetic activity. However, no proper scientific evidence exists to support its antidiabetic property at a mechanistic level. The present study was designed to assess the in-vitro and in-vivo antidiabetic activity of hydroalcoholic extracts of Zingiber officinale rhizome and Centella asiatica leaves. In-vitro assays like alpha amylase as well as alpha glucosidase inhibition assay and glucose uptake by yeast cell assay have been performed. Invivo activity was also evaluated in streptozotocin-induced diabetic albino rats. Acarbose and metformin are taken as standard drugs for comparison. Both the extracts elicited significant antidiabetic activity both in-vitro and in-vivo. The suppression of alpha amylase and alpha glucosidase enzymes is connected with their anti-diabetic action. It also demonstrated its impact by increasing glucose absorption by peripheral tissue and may have insulin memetic action. Although Centella asiatica was slightly more active than Ginger. It is very likely that regular ingestion of these two herbs in conjunction with conventional hypoglycemic medicines will aid in the maintenance of blood glucose levels in diabetic patients. [ABSTRACT FROM AUTHOR]

Drug-induced liver injury (DILI) is the leading cause of compound attrition during drug development. Over the years, a battery of in-vitro cell culture toxicity tests is being conducted to evaluate the toxicity of compounds prior to testing in laboratory animals. Two-dimensional (2D) in-vitro cell culture models are commonly used and have provided a great deal of knowledge; however, these models often fall short in mimicking natural structures of tissues in-vivo. Testing in humans is the most logical method, but unfortunately there are ethical limitations associated with human tests. To overcome these limitations better human-relevant, predictive models are required. The past decade has witnessed significant efforts towards the development of three-dimensional (3D) in-vitro cell culture models better mimicking in-vivo physiology. 3D cell culture has advantages in being representative of the interactions of cells in-vivo and when validated can act as an interphase between 2D cell culture models and in-vivo animal models. The current review seeks to provide an overview of the challenges that make biomarkers used for detection of DILI not to be sensitive enough during drug development and explore how 3D cell culture models can be used to address the gap with the current models. [ABSTRACT FROM AUTHOR]

Botanicals have become a very important part of our life and are increasingly used as a primary source of actives in pharmaceuticals, cosmetics, nutraceuticals and personal care products. Extensive studies have been conducted on botanicals to understand their chemical profile and most of them have a history of safe use. Technical advances to isolate the bioactives, determine their molecular structure as well as their mechanism of action has generated considerable data and are available in the form of scientific publications as well as filing of patents. In this review, we aim to present the information pertaining to therapeutic applications of bioactives from different medicinal plants as disclosed in filed and granted patents to one of the largest publicly funded organizations in India namely Council of Scientific and Industrial Research (CSIR). The review also presents an assignee focused analysis and provides insights into the level of patent filing activity in the area of bioactives and the therapeutic applications by CSIR, India. Such information can provide a valuable tool for exploiting a firm’s portfolio of patent holdings to assist decision-makers to identify the most valuable patents; product area or business opportunities among its own patent holdings. [ABSTRACT FROM AUTHOR]

Key points 1. Four plain emulgel formulas were prepared and investigated for physiochemical and stability properties (F1–F4). 2. The emulgel F3 exhibited optimum smooth homogeneous consistency, neutral pH, acceptable viscosity, spreadability, extrudability values and best storage stability properties. 3. A murine skin model infected with clinical MRSA isolate was established and wounds were monitored via apparent physical wound healing measurements and histopathological examination. 4. The MF3 containing 4% LRJ and 50% GE has shown the highest in vivo wound healing capacities.

Obsessive–compulsive disorder (OCD) is a commonly encountered psychiatric illness. Cognitive behavior therapy (CBT)/exposure and response prevention (ERP) is first-line treatment option for OCD. When facilities are available, CBT/ERP monotherapy may be recommended in mild to moderately ill patients. However, in severely ill patients, the management comprising CBT and pharmacotherapy is more efficacious than single treatment alone. Behaviorists practicing ERP recommend that exposure in real-life situations (vivo) is more effective than in imaginative situations (vitro). Here, we present a case of a middle-aged female with obsessions regarding contamination by menstrual blood and compulsions of checking and cleaning, causing marked sociooccupational deficit. The index patient who was suffering from debilitating form of OCD failed to respond to pharmacotherapy alone and later with combination of pharmacotherapy; brief in vivo flooding and ERP in vitro responded well; which is sustained at 6 months' follow-up.

Introduction: Cervical cancer is the leading cause of cancer-related death in women, so novel therapeutic approaches are needed to improve the effectiveness of current therapies or extend their activity. In recent decades, graphene analogs, such as Mxene, an emerging class of two-dimensional (2D) graphene analogs, have been drawing considerable attention based on their intrinsic physicochemical properties and performance as potential candidates for tumor therapy, particularly for therapeutic purposes. Here we explored the targeted drug delivery in cervical cancer in in vivo model. Mxene-based nanocarriers are not able to be precisely controlled in cancer treatment.Method: To solve this problem, the titanium carbide-magnetic core-shell nanocarrier (Ti3C2-Fe3O4@SiO2-FA) is also developed to provide synergetic anticancer with magnetic controlling ability along with pH-responsive drug release. A xenograft model of the cervix was used to investigate the effects of Cisplatin alone, or in combination with Ti3C2@FA and Ti3C2@ Fe3O4@SiO2-FA, on tumor growth following histological staining for evaluation of necrosis.Result and Discussion: A significant tumor-growth suppression effect is shown when the Ti3C2-Fe3O4@SiO2-FA nanocarrier is magnetically controlled Cisplatin drug release. It reveals a synergistic therapeutic efficacy used in conjunction with pharmaceuticals (p < .001). According to the in vivo study, the Ti3C2@FA@Cisplatin nanocomposite exhibits less tumor growth than the drug alone or Ti3C2@FA@Cisplatin via increasing necrosis effect (p < .001). Through this study, Mxene nanosheets are expanded for biomedical applications, not only through the fabrication of biocompatible magnetic Mxene nanocomposite but also through the development of functionalization strategies that enable the magnetic Ti3C2 nanocomposite to load high levels of Cisplatin for cervical cancer treatment (242.5%). Hence, Ti3C2-Fe3O4@SiO2-FA nanocarriers would be promising candidates to improve cancer treatment efficiency.

In this study, in vitro/vivo biocompatibility experiments of Mg-Al-Mn alloy were carried out, and AM50 and AM60 alloys were used in the experiments. Immersion and potentiodynamic corrosion have been applied to these alloys in vitro. For biocompatibility, cytotoxicity test was performed. A total of 40 rats were used for the in-vivo experiment. AM series alloys were surgically placed in the femoral condyle as mini screws and monitored radiographically. AM alloys were removed together with the femur at the end of 7 weeks and further examined. After in-vivo application, the biodegradability level was successfully concluded with blood mineral analysis and urinalysis. In this study, the bioprocess of AM series Mg alloys with Al and Mn additions has been completed. As a result, the AM alloys used can be classified as biocompatible and biodegradable materials. [ABSTRACT FROM AUTHOR]