Therapeutic potential and novel formulations of ursolic acid and its derivatives: an updated review.

Plants produce biologically active metabolites that have been utilised to cure a variety of severe and persistent illnesses. There is a possibility that understanding how these bioactive molecules work would allow researchers to come up with better treatments for diseases including malignancy, cardiac disease and neurological disorders. A triterpene called ursolic acid (UA) is a pentacyclic prevalent triterpenoid found in fruits, leaves, herbs and blooms. The biological and chemical aspects of UA, as well as their presence, plant sources and biosynthesis, and traditional and newer technologies of extraction, are discussed in this review. Because of its biological function in the creation of new therapeutic techniques, UA is a feasible option for the evolution and medical management of a wide range of medical conditions, including cancer and other life threatening diseases. Despite this, the substance's poor solubility in aquatic environments makes it unsuitable for medicinal purposes. This hurdle was resolved in many different ways. The inclusion of UA into various pharmaceutical delivery approaches was found to be quite effective in this respect. This review also describes the properties of UA and its pharmacokinetics, as well as therapeutic applications of UA for cancer, inflammatory and cardiovascular diseases, in addition to its anti-diabetic, immunomodulatory, hepatoprotective and anti-microbial properties. Some of the recent findings related to novel nano-sized carriers as a delivery system for UA and the patents related to the applications of UA and its various derivatives are covered in this review. The analytical study of UA, oleanolic acid and other phytoconstituents by UV, HPLC, high-performance thin-layer chromatography and gas chromatography is also discussed. In the future, UA could be explored in vivo using various animal models and, in addition, the regulatory status regarding UA needs to be explored. © 2023 Society of Chemical Industry.

HDAC inhibition prevents hypobaric hypoxia-induced spatial memory impairment through PΙ3K/GSK3ß/CREB pathway.

Hypobaric hypoxia at higher altitudes usually impairs cognitive function. Previous studies suggested that epigenetic modifications are the culprits for this condition. Here, we set out to determine how hypobaric hypoxia mediates epigenetic modifications and how this condition worsens neurodegeneration and memory loss in rats. In the current study, different duration of hypobaric hypoxia exposure showed a discrete pattern of histone acetyltransferases and histone deacetylases (HDACs) gene expression in the hippocampus when compared with control rat brains. The level of acetylation sites in histone H2A, H3 and H4 was significantly decreased under hypobaric hypoxia exposure compared to the control rat's hippocampus. Additionally, inhibiting the HDAC family with sodium butyrate administration (1.2 g/kg body weight) attenuated neurodegeneration and memory loss in hypobaric hypoxia-exposed rats. Moreover, histone acetylation increased at the promoter regions of brain-derived neurotrophic factor (BDNF); thereby its protein expression was enhanced significantly in hypobaric hypoxia exposed rats treated with HDAC inhibitor compared with hypoxic rats. Thus, BDNF expression upregulated cAMP-response element binding protein (CREB) phosphorylation by stimulation of PI3K/GSK3ß/CREB axis, which counteracts hypobaric hypoxia-induced spatial memory impairment. In conclusion, these results suggested that sodium butyrate is a novel therapeutic agent for the treatment of spatial memory loss associated with hypobaric hypoxia, and also further studies are warranted to explore specific HDAC inhibitors in this condition.

Cross-cultural adaptation and psychometric properties of the Hindi version of Child Perception Questionnaire (CPQ11-14 ) in school children.

BACKGROUND: There is a need to validate OHRQoL measures in Hindi to assess the OHRQoL of Indian children. AIM: To develop a Hindi version of the CPQ11-14 and to appraise its validity and reliability for use among North Indian children aged 11-14 years. DESIGN: The cross-culturally adapted Hindi version of CPQ11-14 was achieved by forward translation, backward translation, committee review, and pretesting. A total of 1000 children were recruited from schools, chosen by two-stage cluster random sampling technique. After completing the self-administered questionnaire CPQ11-14 by the child, oral examination was conducted using decayed/missing/filled teeth (DMFT) index, malocclusion index, and Dean's fluorosis index. Test-retest reliability was checked on 100 participants after one week. RESULTS: The floor effect was present in 3.6% individuals, and there was no ceiling effect. Cronbach's alpha for the overall CPQ11-14 scale was 0.963. Intra-class correlation (ICC) coefficient was 0.952 for the entire scale. Cronbach's alpha value for test-retest was 0.918. There was a non-significant change in domain-level and overall median CPQ11-14 scores with an increase in DMFT scores. For malocclusion and fluorosis, there was a statistically significant increase in overall and domain-level scores with increased severity scores. CPQ11-14 and individual domains significantly correlated with both the global questions. CONCLUSION: Hindi version of CPQ11-14 is a reliable scale to assess OHRQoL in Hindi speaking 11- to 14-year-old children.

Perceptions of a university's faculty members on organ donation.

Background: . Availability of donated organs may save lives of people with end-stage disease. However, multiple barriers exist for obtaining donated organs such as insufficient knowledge and lack of a positive attitude towards organ donation. We assessed the knowledge and attitude regarding organ donation among faculty members of a university in India. Methods: . We did this observational, cross-sectional study from December 2017 to January 2018. A structured, close-ended questionnaire consisting of 20 items was used to assess knowledge, attitude and practices regarding organ donation. Data for 170 participants were analysed using SPSS version 21. Unpaired t-test was used to compare the knowledge and attitude score among different variables. Results: . A statistically significant difference was found between the attitude score of graduate and postgraduate faculty (p=0.003), as well as between graduate and doctoral faculty (p=0.001). We found that 5.3% of participants had already donated organs, 12.9% had pledged to donate and 63.5% of participants had expressed willingness to donate organs. Conclusions: . There is a need to increase the knowledge regarding organ donation as most people have a good attitude towards organ donation, but their knowledge was insufficient and at times inaccurate.

Intersubband Quantum Disc-in-Nanowire Photodetectors with Normal-Incidence Response in the Long-Wavelength Infrared.

Semiconductor nanowires have great potential for realizing broadband photodetectors monolithically integrated with silicon. However, the spectral range of such detectors has so far been limited to selected regions in the ultraviolet, visible, and near-infrared regions. Here, we report on the first intersubband nanowire heterostructure array photodetectors exhibiting a spectrally resolved photoresponse from the visible to long-wavelength infrared. In particular, the infrared response from 3 to 20 µm is enabled by intersubband transitions in low-bandgap InAsP quantum discs synthesized axially within InP nanowires. The intriguing optical characteristics, including unexpected sensitivity to normal incident radiation, are explained by excitation of the longitudinal component of optical modes in the photonic crystal formed by the nanostructured portion of the detectors. Our results provide a generalizable insight into how broadband nanowire photodetectors may be designed and how engineered nanowire heterostructures open up new, fascinating opportunities for optoelectronics.

Room-temperature InP/InAsP Quantum Discs-in-Nanowire Infrared Photodetectors.

The possibility to engineer nanowire heterostructures with large bandgap variations is particularly interesting for technologically important broadband photodetector applications. Here we report on a combined study of design, fabrication, and optoelectronic properties of infrared photodetectors comprising four million n+-i-n+ InP nanowires periodically ordered in arrays. The nanowires were grown by metal-organic vapor phase epitaxy on InP substrates, with either a single or 20 InAsP quantum discs embedded in the i-segment. By Zn compensation of the residual n-dopants in the i-segment, the room-temperature dark current is strongly suppressed to a level of pA/NW at 1 V bias. The low dark current is manifested in the spectrally resolved photocurrent measurements, which reveal strong photocurrent contributions from the InAsP quantum discs at room temperature with a threshold wavelength of about 2.0 µm and a bias-tunable responsivity reaching 7 A/W@1.38 µm at 2 V bias. Two different processing schemes were implemented to study the effects of radial self-gating in the nanowires induced by the nanowire/SiOx/ITO wrap-gate geometry. Summarized, our results show that properly designed axial InP/InAsP nanowire heterostructures are promising candidates for broadband photodetectors.

The malleable brain: plasticity of neural circuits and behavior - a review from students to students.

One of the most intriguing features of the brain is its ability to be malleable, allowing it to adapt continually to changes in the environment. Specific neuronal activity patterns drive long-lasting increases or decreases in the strength of synaptic connections, referred to as long-term potentiation and long-term depression, respectively. Such phenomena have been described in a variety of model organisms, which are used to study molecular, structural, and functional aspects of synaptic plasticity. This review originated from the first International Society for Neurochemistry (ISN) and Journal of Neurochemistry (JNC) Flagship School held in Alpbach, Austria (Sep 2016), and will use its curriculum and discussions as a framework to review some of the current knowledge in the field of synaptic plasticity. First, we describe the role of plasticity during development and the persistent changes of neural circuitry occurring when sensory input is altered during critical developmental stages. We then outline the signaling cascades resulting in the synthesis of new plasticity-related proteins, which ultimately enable sustained changes in synaptic strength. Going beyond the traditional understanding of synaptic plasticity conceptualized by long-term potentiation and long-term depression, we discuss system-wide modifications and recently unveiled homeostatic mechanisms, such as synaptic scaling. Finally, we describe the neural circuits and synaptic plasticity mechanisms driving associative memory and motor learning. Evidence summarized in this review provides a current view of synaptic plasticity in its various forms, offers new insights into the underlying mechanisms and behavioral relevance, and provides directions for future research in the field of synaptic plasticity. Read the Editorial Highlight for this article on page 788. Cover Image for this issue: doi: 10.1111/jnc.13815.

Defect-induced infrared electroluminescence from radial GaInP/AlGaInP quantum well nanowire array light- emitting diodes.

Radial GaInP/AlGaInP nanowire array light-emitting diodes (LEDs) are promising candidates for novel high-efficiency solid state lighting due to their potentially large strain-free active emission volumes compared to planar LEDs. Moreover, by proper tuning of the diameter of the nanowires, the fraction of emitted light extracted can be significantly enhanced compared to that of planar LEDs. Reports so far on radial growth of nanowire LED structures, however, still point to significant challenges related to obtaining defect-free radial heterostructures. In this work, we present evidence of optically active growth-induced defects in a fairly broad energy range in vertically processed radial GaInP/AlGaInP quantum well nanowire array LEDs using a variety of complementary experimental techniques. In particular, we demonstrate strong infrared electroluminescence in a spectral range centred around 1 eV (1.2 µm) in addition to the expected red light emission from the quantum well. Spatially resolved cathodoluminescence studies reveal a patchy red light emission with clear spectral features along the NWs, most likely induced by variations in QW thickness, composition and barriers. Dark areas are attributed to infrared emission generated by competing defect-assisted radiative transitions, or to trapping mechanisms involving non-radiative recombination processes. Possible origins of the defects are discussed.

Bias-dependent spectral tuning in InP nanowire-based photodetectors.

Nanowire array ensembles contacted in a vertical geometry are extensively studied and considered strong candidates for next generations of industrial scale optoelectronics. Key challenges in this development deal with optimization of the doping profile of the nanowires and the interface between nanowires and transparent top contact. Here we report on photodetection characteristics associated with doping profile variations in InP nanowire array photodetectors. Bias-dependent tuning of the spectral shape of the responsivity is observed which is attributed to a Schottky-like contact at the nanowire-ITO interface. Angular dependent responsivity measurements, compared with simulated absorption spectra, support this conclusion. Furthermore, electrical simulations unravel the role of possible self-gating effects in the nanowires induced by the ITO/SiO x wrap-gate geometry. Finally, we discuss possible reasons for the observed low saturation current at large forward biases.

Radial Nanowire Light-Emitting Diodes in the (AlxGa1-x)yIn1-yP Material System.

Nanowires have the potential to play an important role for next-generation light-emitting diodes. In this work, we present a growth scheme for radial nanowire quantum-well structures in the AlGaInP material system using a GaInP nanowire core as a template for radial growth with GaInP as the active layer for emission and AlGaInP as charge carrier barriers. The different layers were analyzed by X-ray diffraction to ensure lattice-matched radial structures. Furthermore, we evaluated the material composition and heterojunction interface sharpness by scanning transmission electron microscopy energy dispersive X-ray spectroscopy. The electro-optical properties were investigated by injection luminescence measurements. The presented results can be a valuable track toward radial nanowire light-emitting diodes in the AlGaInP material system in the red/orange/yellow color spectrum.

III-V nanowire synthesis by use of electrodeposited gold particles.

Semiconductor nanowires are great candidates for building novel electronic devices. Considering the cost of fabricating such devices, substrate reuse and gold consumption are the main concerns. Here we report on implementation of high throughput gold electrodeposition for selective deposition of metal seed particles in arrays defined by lithography for nanowire synthesis. By use of this method, a reduction in gold consumption by a factor of at least 300 was achieved, as compared to conventional thermal evaporation for the same pattern. Because this method also facilitates substrate reuse, a significantly reduced cost of the final device is expected. We investigate the morphology, crystallography, and optical properties of InP and GaAs nanowires grown from electrodeposited gold seed particles and compare them with the properties of nanowires grown from seed particles defined by thermal evaporation of gold. We find that nanowire synthesis, as well as the material properties of the grown nanowires are comparable and quite independent of the gold deposition technique. On the basis of these results, electrodeposition is proposed as a key technology for large-scale fabrication of nanowire-based devices.

A comparative study of absorption in vertically and laterally oriented InP core-shell nanowire photovoltaic devices.

We have compared the absorption in InP core-shell nanowire p-i-n junctions in lateral and vertical orientation. Arrays of vertical core-shell nanowires with 400 nm pitch and 280 nm diameter, as well as corresponding lateral single core-shell nanowires, were configured as photovoltaic devices. The photovoltaic characteristics of the samples, measured under 1 sun illumination, showed a higher absorption in lateral single nanowires compared to that in individual vertical nanowires, arranged in arrays with 400 nm pitch. Electromagnetic modeling of the structures confirmed the experimental observations and showed that the absorption in a vertical nanowire in an array depends strongly on the array pitch. The modeling demonstrated that, depending on the array pitch, absorption in a vertical nanowire can be lower or higher than that in a lateral nanowire with equal absorption predicted at a pitch of 510 nm for our nanowire geometry. The technology described in this Letter facilitates quantitative comparison of absorption in laterally and vertically oriented core-shell nanowire p-i-n junctions and can aid in the design, optimization, and performance evaluation of nanowire-based core-shell photovoltaic devices.

Yersinia pestis uses the Ail outer membrane protein to recruit vitronectin.

Yersinia pestis, the agent of plague, requires the Ail (attachment invasion locus) outer membrane protein to survive in the blood and tissues of its mammalian hosts. Ail is important for both attachment to host cells and for resistance to complement-dependent bacteriolysis. Previous studies have shown that Ail interacts with components of the extracellular matrix, including fibronectin, laminin and heparan sulfate proteoglycans, and with the complement inhibitor C4b-binding protein. Here, we demonstrate that Ail-expressing Y. pestis strains bind vitronectin - a host protein with functions in cell attachment, fibrinolysis and inhibition of the complement system. The Ail-dependent recruitment of vitronectin resulted in efficient cleavage of vitronectin by the outer membrane Pla (plasminogen activator protease). Escherichia coli DH5α expressing Y. pestis Ail bound vitronectin, but not heat-treated vitronectin. The ability of Ail to directly bind vitronectin was demonstrated by ELISA using purified refolded Ail in nanodiscs.

Effect of modified atmospheric packaging on the shelf life of Kalakand and its influence on microbial, textural, sensory and physico-chemical properties.

Kalakand, a popular traditional milk sweet of Indian sub-continent, was packaged under air and modified atmospheric packaging (MAP) conditions (98 % N2, 98 % CO2 and 50 % N2: 50 % CO2). The samples were stored at 10, 25 and 37 °C and evaluated for various physico-chemical, microbial, textural and sensory changes, in order to establish the applicability of MAP for storage of Kalakand. It could be established that the MAP conditions of 50 % N2: 50 % CO2and storage at 10 °C, were the most suitable conditions for preserving the Kalakand for upto 60 days.

Antinociceptive and anti-inflammatory activities of Bridelia retusa methanolic fruit extract in experimental animals.

Antinociceptive and anti-inflammatory potentials of methanolic extract of Bridelia retusa fruit (BRME) were evaluated against different animal models in rodents. Antinociceptive effects of BRME were assessed in mice using the acetic acid-induced writhing and formalin test. Anti-inflammatory effects of BRME in three different doses, namely, 100, 200, and 400 mg/kg, were evaluated by utilizing different animal models representing various changes associated with inflammation, namely, carrageenan-induced paw oedema, histamine and serotonin-induced paw oedema, arachidonic acid-induced paw oedema, formalin-induced paw oedema, TPA-induced ear oedema, acetic acid-induced vascular permeability, total WBC count in paw fluid, and myeloperoxidase assay. Also BRME was phytochemically evaluated using chromatographic method. The BRME did not exhibit any signs of toxicity up to a dose of 2000 mg/kg. The extract showed statistical significant inhibition of induced nociception and inflammation in dose dependent manner. The higher dose of extract significantly inhibited pain and inflammation against control (P < 0.001). HPLC results revealed the presence of gallic acid and ellagic acid as phytoconstituents in BRME and it was proven as anti-inflammatory agents. The present study scientifically demonstrated the antinociceptive and anti-inflammatory potential of fruit of B. retusa methanolic extract. These effects may be attributed to the presence of polyphenolic phytoconstituents in the extract.

Formulation and Development of Novel Sulfasalazine Bilayer Tablets for The Treatment of Arthritis Associated With IBD: In-vitro and In-vivo Investigations.

Sulfasalazine needs frequent daily dosing and the administration of numerous tablets per day pose challenges to patient compliance, contributing to increased adverse effects and difficulties in disease control. These inconveniences result in less effective treatment for arthritis associated with inflammatory bowel disease i.e. ulcerative colitis etc. To improve drug bioavailability, a delayed-release mechanism that releases the drug at the colon is necessary. To develop and optimize colon-targeted controlled release bilayer tablets coated with pH-dependent polymers. The bilayer tablets containing the immediate release part and sustained release part were developed. The tablets were coated with enteric-coated with Eudragit® S-100 and l-100 to achieve release in the colon. Granule properties and tablets were evaluated. The physicochemical parameters of the tablets were evaluated including, stability study, and drug release in 0.1 N HCl (pH 1.2), pH 6.8 phosphate buffer, pH 7.4 phosphate buffer for 2, 1, and up to 24 h respectively. Radiographic imaging and in vivo pharmacokinetic studies were also done in Rabbits. The bilayer tablets containing immediate and sustained release were successfully developed for the colon targeting. The granule properties were found within the acceptable range indicating good flow properties. The physicochemical properties of the tablets were also found acceptable. The tablets did not show release in 0.1 N HCl and 6.8 phosphate buffer but drug release was found under control in the 7.4 pH buffer. Sulfasalazine coated bilayer tablets were found stable and no significant changes were observed in the stability studies. Based on the X-ray studies, the formulated tablet remained discernible in the stomach, small intestine, and colon for a duration of up to 24 h. Finally, by the 32nd hour, the tablet was no longer visible in the X-ray examination, leading to the conclusion of complete drug release. The drug concentration in plasma remained within the therapeutic range for up to 24 h in vivo. These novel formulations present substantial advantages, providing prolonged targeted drug release and reducing systemic adverse effects. The results suggest promising potential for treating arthritis in Inflammatory bowel disease (IBD) patients, offering a solution to current delivery systems.

Fully flexible implantable neural probes for electrophysiology recording and controlled neurochemical modulation.

Targeted delivery of neurochemicals and biomolecules for neuromodulation of brain activity is a powerful technique that, in addition to electrical recording and stimulation, enables a more thorough investigation of neural circuit dynamics. We have designed a novel, flexible, implantable neural probe capable of controlled, localized chemical stimulation and electrophysiology recording. The neural probe was implemented using planar micromachining processes on Parylene C, a mechanically flexible, biocompatible substrate. The probe shank features two large microelectrodes (chemical sites) for drug loading and sixteen small microelectrodes for electrophysiology recording to monitor neuronal response to drug release. To reduce the impedance while keeping the size of the microelectrodes small, poly(3,4-ethylenedioxythiophene) (PEDOT) was electrochemically coated on recording microelectrodes. In addition, PEDOT doped with mesoporous sulfonated silica nanoparticles (SNPs) was used on chemical sites to achieve controlled, electrically-actuated drug loading and releasing. Different neurotransmitters, including glutamate (Glu) and gamma-aminobutyric acid (GABA), were incorporated into the SNPs and electrically triggered to release repeatedly. An in vitro experiment was conducted to quantify the stimulated release profile by applying a sinusoidal voltage (0.5 V, 2 Hz). The flexible neural probe was implanted in the barrel cortex of the wild-type Sprague Dawley rats. As expected, due to their excitatory and inhibitory effects, Glu and GABA release caused a significant increase and decrease in neural activity, respectively, which was recorded by the recording microelectrodes. This novel flexible neural probe technology, combining on-demand chemical release and high-resolution electrophysiology recording, is an important addition to the neuroscience toolset used to dissect neural circuitry and investigate neural network connectivity.

Prepancreatic postduodenal portal vein: a rare vascular variant detected on imaging.

Anomalous preduodenal portal vein is a rare abdominal vascular variant; even rarer is the prepancreatic postduodenal position. We report an anomalous portal vein positioned in between duodenum and pancreatic head detected on contrast enhanced computed tomography. Awareness and accurate radiological interpretation of this unique and rare vascular pattern can prevent inadvertent injury during surgical and radiological interventions.

Celiacomesenteric trunk: a short report.

The authors describe the case of a 44-year-old male with chronic liver disease in whom celiacomesenteric trunk (CMT) was incidentally detected on routine multidetector row computed tomography of abdomen. The CMT (measuring approximately in diameter 12.3 mm) divided into celiac trunk and superior mesenteric artery (SMA) (measuring approximately 7.5 and 7.2 mm, respectively). The celiac trunk further divided into common hepatic, left gastric, and right inferior phrenic and splenic arteries. The common hepatic artery gave off gastroduodenal arteries before continuing as hepatic artery proper. The SMA was seen running down, deep to the neck of the pancreas to supply the midgut. The incidence and clinical implications of this vascular variation are discussed with a review of the relevant literature.

Effect of electric field direction on neuronal activity: an ex-vivo study.

The effect of electrical stimulation on neurons depends on the spatiotemporal properties of the applied electric field as well as on the biophysical properties of the neural tissue, which includes geometric and electrical characteristics of the cells, and the neural circuit dynamics. In this work, we characterize the effect of electric field direction on neural response in cortical layers. This can, for instance, enable more efficient (e.g., with reduced currents) and/or more selective stimulation. We stimulated mice brain slices using a recently developed brain slice platform to study transcranial currents in an ex-vivo model, where electrodes are separated from the brain slice to inject electric fields at a distance. By rotating the electrode array with respect to the slice, we changed the direction of electric field with respect to the cortical column. Our results demonstrate that in somatosensory cortex, the maximum local field potential (LFP) response is attained when the electric field is oriented parallel to the cortical column. For the same field intensity, when the field is oriented perpendicular to the cortical column, the LFP response is absent. This confirms that electric field direction is an important quantity to determine the effect of neuronal stimulation.