Enhancement of dual zero phonon line emissions in nanodiamonds using quasiperiodic photonic structures.

Color centers in nanodiamonds (NDs) have been largely explored by coupling to a photonic structured matrix (PSM) to amplify visible range emission features, enhancing their use in quantum technologies. Here, we study the emission enhancement of dual near-infrared zero phonon line (ZPL) emission from silicon-boron (SiB) and silicon-vacancy (SiV-) centers in NDs using a spontaneously emerged low index-contrast quasiperiodic PSM, having micron-scale air pores. An intensity enhancement factor of 6.15 for SiV- and 7.8 for SiB ZPLs is attained for the PSM sample compared to a control sample. We find Purcell enhancement of 2.77 times for the PSM sample using spatial-dependent decay rate measurements, supported by localized field intensity confinement in the sample. Such cavity-like emission enhancement and lifetime reduction are enabled by an in-plane order-disorder scattering in the PSM sample substantiated by pump-dependent emission measurements. The results put forward a facile approach to tailor the near-infrared dual ZPL emission from NDs using nanophotonic structures.

Intranasal (2R, 6R)-hydroxynorketamine for acute pain: Behavioural and neurophysiological safety analysis in mice.

Ketamine is known for its antinociceptive effect and is also used for treatment-resistant depression. However, the efficacy and safety of (2R, 6R)-hydroxynorketamine (HNK), a ketamine metabolite has been sparingly investigated for acute pain management. The current study aims at investigating the antinociceptive effect of intranasal (2R, 6R)-HNK using pre-clinical models of acute pain. Additionally, the behavioural and neurophysiological safety analyses were carried out for the effective time window. Antinociceptive efficacy of (2R, 6R)-HNK was evaluated using the hot plate test and Hargreaves' plantar test. The formalin test was carried out in both the acute and tonic phases. The neurophysiological and behavioural safety analyses were carried out separately for the haemodynamic function, cortical electroencephalography (EEG), and spontaneous behavioural functions. Analgesic effect of (2R, 6R)-HNK was evident by a significant increase in paw-withdrawal latency in both Hargreaves' and hot plate tests. Additionally, the (2R, 6R)-HNK showed a significant ameliorative effect on pain-related behaviour in the second phase of the formalin test. (2R, 6R)-HNK exhibited an anxiolytic effect without causing any significant changes in locomotor activity and haemodynamic parameters. Power spectral density (PSD) analysis of electroencephalogram revealed no significant changes except a comparative increase in the gamma band range. Both the locomotor functions in the open field test and the PSD value of delta wave indicated no sedative effect at the given dose of (2R, 6R)-HNK. The results demonstrated the pain-alleviating effect of (2R, 6R)-HNK without compromising the neurophysiological and behavioural function. Therefore, intranasal (2R, 6R)-HNK is suggested as a safe candidate for further clinical study in the management of acute pain.

Intranasal Ketamine for Acute Pain: Behavioral and Neurophysiological Safety Analysis in Mice.

BACKGROUND: Subanesthetic ketamine has been used for treatment-resistant depression and is popular as an opioid-sparing agent. OBJECTIVE: The present study aimed to investigate the dose-dependent antinociceptive effect of intranasal ketamine (INK) along with behavioral and neurophysiological safety in mice. METHODS: Antinociceptive efficacy was evaluated in the terms of thermal nociceptive response and formalin test. The safety studies were carried out separately in healthy mice using telemetry-based cortical electroencephalography, hemodynamic changes, and spontaneous behavioral functions, including anxiety, stereotypic movement, and locomotor functions. RESULTS: INK administration significantly augmented the thermal nociceptive threshold and alleviated the pain response in the tonic phase of the formalin test. The results showed the dose-independent effectiveness of ketamine for thermal nociceptive responses because there were no significant differences among different INK dose groups. Behavioral safety analysis using the open field exploratory test revealed no significant effect of INK on anxiety-like functions in healthy mice. However, INK mice showed significantly more stereotypic movement but slower locomotor activities. The electroencephalography signal power spectrum density analysis revealed no significant changes by INK administration except a lower value in the α range. No significant changes were reported in heart rate, diastolic blood pressure, or systolic blood pressure at the higher dose equivalent used in the pain model. CONCLUSIONS: The study demonstrated the behavioral and neurophysiological safety of INK, although it had a mild sedative effect. Therefore, INK is suggested as a potentially safe candidate for the management of acute pain. (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX)© 2021 Elsevier HS Journals, Inc.

Blood-stage antimalarial activity, favourable metabolic stability and in vivo toxicity of novel piperazine linked 7-chloroquinoline-triazole conjugates.

The persistence of drug resistance poses a significant obstacle to the advancement of efficacious malaria treatments. The remarkable efficacy displayed by 1,2,3-triazole-based compounds against Plasmodium falciparum highlights the potential of triazole conjugates, with diverse pharmacologically active structures, as potential antimalarial agents. We aimed to synthesize 7-dichloroquinoline-triazole conjugates and their structure-activity relationship (SAR) derivatives to investigate their anti-plasmodial activity. Among them, QP11, featuring a m-NO2 substitution, demonstrated efficacy against both chloroquine-sensitive and -resistant parasite strains. QP11 selectively inhibited FP2, a cysteine protease involved in hemoglobin degradation, and showed synergistic effects when combined with chloroquine. Additionally, QP11 hindered hemoglobin degradation and hemozoin formation within the parasite. Metabolic stability studies indicated high stability of QP11, making it a promising antimalarial candidate. In vivo evaluation using a murine malaria model demonstrated QP11's efficacy in eradicating parasite growth without neurotoxicity, presenting it as a promising compound for novel antimalarial development.

Phytochemistry and pharmacology of Celastrus paniculatus Wild.: a nootropic drug.

OBJECTIVES: Celastrus paniculatus Wild is an evergreen climbing shrub. The plant is of great significance in the traditional Indian System of Medicine, such as Ayurveda, Unani, and Siddha. The seeds and their oil are extensively used to treat neurological disorders such as cognitive dysfunction, paralysis, epilepsy, insomnia, and other ailments like rheumatism, arthritis, sciatica, and leprosy. This paper aims to highlight the nootropic activity of C. paniculatus and explore its phytochemistry, traditional uses, and other pharmacological activities. METHODS: All available information concerning C. paniculatus has been searched in the internationally accepted scientific databases, including PubMed, ScienceDirect, Scopus, and Google Scholar. Additional knowledge was gathered from the classical Textbooks and Unani Pharmacopoeia. RESULTS: C. paniculatus is a rich source of several secondary metabolites, such as ß-Dihydroagarofuranoids sesquiterpenes, alkaloids (Celastrine, Celapanin, Celapagin, and paniculatin), flavonoids, terpenoid (ß-amyrin, Lupeol, Pristimerin), sterols (ß-sitosterol, campesterol, stigmasterol, α-tocopherol, γ-Tocopherol), fatty acid (palmitic, stearic, oleic, linoleic, linolenic acids) and non-fatty acids (Benzoic acid, Cinnamic acid). The various study shows that the extracts and active constituent of this plant possess potent nootropic activity. Besides nootropic activity, it has also been reported for anti-Alzheimer, anticonvulsant, antidepressant, antioxidant, analgesic, anti-inflammatory, antiarthritic, gastroprotective, anti-psoriatic, wound healing, antibacterial, antimalarial, and several other properties. CONCLUSIONS: Several in vitro and in vivo trials confirm the conventional use of C. paniculatus in cognitive dysfunction. However, the relations between the possible mechanisms of other activities and traditional uses of the C. paniculatus remain indistinct. Still, pharmacological studies also explored the effects of C. paniculatus, which were not recognized in ancient times, such as cytotoxic, ACE inhibitor, and antidiabetic activities. These discoveries are may be beneficial in the development of the new drug to treat various diseases. It is also confirmed that the ß-dihydroagarofuranoids exhibit significant AChE inhibitory, cytotoxic, antibacterial, and insecticidal effects. This versatile medicine is truly a life elixir. Considering the therapeutic importance of the C. paniculatus and the absence of any reported clinical studies, extensive clinical trials are needed to explore its memory enhancing and other activities.

Concept of dementia (Nisy a n) in Unani system of medicine and scientific validation of an important Unani pharmacopoeial preparation 'Majoon Vaj' for its management: a review.

OBJECTIVES: This review focused on the concept of dementia in the Unani system of medicine and comprehensive, updated information on Majoon Vaj about the phytochemistry, nootropic, CNS activities and provide insights into potential opportunities for future research. METHODS: The classical literature on Majoon Vaj for its anti-dementic properties, and therapeutic uses were gathered from nearly thirteen classical Unani books including Unani Pharmacopoeia. The information of pharmacognosy, phytochemical and pharmacological activities of Majoon Vaj and its ingredient was collected by browsing the Internet (PubMed, ScienceDirect, Wiley online library, Google Scholar, ResearchGate). The relevant primary sources were probed, analysed, and included in this review. The keywords used to browse were Majoon Vaj, Dementia, Nootropic, Acorus calamus, Piper nigram, Zingiber officinalis, Nigella sativa, Carum carvi, Plumbago zeylanica, and ß-asarone. Relevant Sources were gathered up to July 2021, and the chemical structures were drawn using ACD/ChemSketch software. The species name and synonyms were checked with WFO (2021): World Flora online (http://www.worldfloraonline.org) an updated version of 'The Plant List.' RESULTS: Majoon Vaj contains an excess of bioactive compounds e.g., alkaloids, phenols, flavonoids, tannins, diterpenes, coumarins, carbohydrates, and fixed oils and its ingredients possess broad pharmacological properties, including cognitive-enhancing, neuroprotective, anti-inflammatory, antioxidant and antimicrobial properties. CONCLUSIONS: The literature of Unani medicine is quite rich in discussing the pathophysiological basis of memory disorders. It argues that memory, retention, and retrieval are regulated by a complex process involving various faculties. Majoon Vaj seems to have great potential for therapeutic applications in the treatment of dementia and thus encourage more preclinical and clinical trials in this field.

Serum biomarkers based neurotrauma severity scale: a study in the mice model of fluid percussion injury.

The study aimed to investigate the significance of serum biomarkers in the severity grading of traumatic brain injury (TBI). For this purpose, mice underwent fluid percussion injury (FPI) at three discrete severity levels, mild, moderate, and severe. The severity of trauma was verified by the qualitative and quantitative histopathology of the brain. The serum samples were analyzed for the potential changes in ubiquitin C­terminal hydrolase­1 (UCHL­1), S100ß, interleukin­6 (IL­6), corticosterone, and ß­endorphin at 24 and 72 h post injury. A multifold increase in the values of UCHL­1 was reported at all severity extents of FPI. However, TBI severity­dependent increase in UCHL­1 was reported on 72 h following FPI but not at 24 h. S100ß values were significantly augmented in the mild and moderate group at both the time point but not in the severe group. Serum level of IL­6 was significantly increased in the mild injury group at 24 h but not in the moderate and severe. At 72 h, IL­6 showed a reverse trend. ß­endorphin and corticosterone were sensitive at an early stage only. Such unique dynamics of each biomarker enable us to propose TBI severity scale in the term of biomarkers codes to predict the extent of neurotrauma. Our preclinical study presents a predictive model for further clinical validation.

Clinical relevance of chronic neuropathic pain phenotypes in mice: A comprehensive behavioral analysis.

Despite a large number of preclinical studies performed each year, the safe and effective therapeutic interventions for chronic pain are scant. Therefore, it appears that pre-clinical modeling requires a systematically organized behavioral test paradigm to quantify the response of animals for a specific pain state. The present study, therefore, conceptualized a test battery to evaluate the behavioral changes in mice following neuropathic pain. We employed sciatic nerve chronic constriction injury (CCI) in C57BL/6 J mice to model chronic pain state. Mice were monitored for thermal hyperalgesia and grip strength for 30 days. Subsequently, mice underwent a behavioral test battery consisting of the nociceptive threshold, the affective and cognitive functions and motor coordination, and strength. Our results showed that CCI mice are insensitive to thermal stimuli. However, nerve-injured mice showed significant changes in neuromuscular coordination, basal anxiety, and hedonic state. Such impaired neuromuscular coordination is indicative of disability rather than the actual pain phenotype. While using the digital gait analysis, our study revealed rationales for the insensitivity of CCI mice to thermal stimuli. Our results suggest that the predictive validity of the CCI model necessitates a comprehensive behavioral test battery to select the clinically relevant and measurable phenotype to quantify chronic neuropathic pain.

Aatrilal (Ammi majus L.), an important drug of Unani system of medicine: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Ammi majus L. (Aatrilal) a member of the family Apiaceae, is native to Egypt and widely distributed in Europe, the Mediterranean, and West Asia. It has been used for the treatment of various dermatological disorders particularly vitiligo in the Unani system of Medicine for ages. In traditional medicine, fruits are used as an emmenagogue as well as a diuretic, blood purifier and to treat leprosy, urinary and digestive disorders. AIM OF THE REVIEW: This paper aims to highlight the medicinal properties of Aatrilal in view of its temperament and phytoconstituents; to signify its potential in the treatment of vitiligo and other ailments as mentioned in Unani system of medicine and also to explore its phytochemistry, pharmacological and clinical studies. MATERIALS AND METHODS: Aatrilal was explored in classical Unani literature for its temperament (mizaj), medicinal properties and therapeutic uses. Published works available on PubMed, Science Direct, and Google Scholar were referred to collect all the available information regarding its phytochemicals and pharmacological studies. All relevant articles up to 2020 were referred including 15 classical Unani books, 15 English books, 72 research, and 3 review papers. The plant's scientific names were validated using 'The Plant List' (www.theplantlist.org). Standard Unani Medical Terminology published by Central Council for Research in Unani Medicine in collaboration with the World Health Organization was used to describe the appropriate Unani terminologies. Glossary of Indian Medicinal Plants and different indexed journals were consulted for botanical and English names. RESULTS: Aatrilal has been used in traditional medicine for ages. Due to controversies in its identity, it was adulterated and substituted with many drugs. The real identity of Aatrilal is now established as the fruit of A. majus L. Despite having numerous pharmacological activities, it is considered the first-line drug for the treatment of vitiligo. It is a rich source of furanocoumarins (xanthotoxin, also known as 8-methoxypsoralen, bergapten, imperatorin, isopimpinellin) with other compounds viz. flavonoids, terpenoids, proteins, essential oil constituents, etc. It has been reported for anti-inflammatory, analgesic, antibacterial, antiviral, cytotoxic, and many other activities. Clinical trials have shown the therapeutic potential in vitiligo and other skin disorders. CONCLUSION: Based on the available literature, it can be concluded that Aatrilal is a drug that has been effectively used in Unani system of medicine for centuries to treat the cases of vitiligo and other dermatological disorders. It has been studied extensively for its phytopharmacological properties. Raw extracts of A. majus form the crux of the main research. Many potentially bioactive compounds are included in the essential oil, but to our knowledge, no detailed studies of its biological activity are yet available. Therefore, our suggestion is to focus future research on essential oil and its ingredients.

Low-pressure fluid percussion minimally adds to the sham craniectomy-induced neurobehavioral changes: Implication for experimental traumatic brain injury model.

Modeling experimental traumatic brain injury (TBI) in rodents is necessarily required to understand the pathophysiological and neurobehavioral consequences of neurotrauma. Numerous models have been developed to study experimental TBI. Fluid percussion injury (FPI) is the most extensively used model to represent clinical phenotypes. Nevertheless, the surgical 'sham' procedure (craniectomy), a prerequisite of FPI, is the impeding factor in experimental TBI. We hypothesized that if craniectomy causes substantial structural and functional changes in the brain, it might mimic the mild FPI-induced neurobehavioral dysfunctions. To understand the hypothesis, C57BL/6 mice were exposed to lateral FPI at 1.2 atm pressure and changes in the neuronal architecture, hippocampal neurogenesis, neuroinflammation, and behavioral functions were compared to the sham (craniectomy) and control mice at day 7 post-FPI. We observed that both the craniectomy and FPI significantly augmented the ipsilateral hippocampal neurogenesis as evaluated by DCX and Beta-III tubulin immunoreactivity. Similarly, a significant increase in GFAP and TMEM immunoreactivity in CA1 and CA3 regions showed that craniectomy mimics FPI-induced neuroinflammation. The additive damaging effect of craniectomy with FPI was also reported in the term of axonal and dendritic fragmentation, swelling and neuronal death using silver staining, Fluoro-jade, and MAP-2 immunoreactivity. Sham-exposed mice showed a significant functional decrease in grip strength. Our results indicate that sham craniectomy itself is enough to cause TBI like characteristics, and thus fluid percussion at mild pressure is minimally additive with craniectomy. Considering the method as a mixed (focal & diffused) injury model, the 'net neurotrauma severity' should be compared with naïve control instead of the sham as it is an outcome of cumulative damage due to fluid pressure and craniectomy. Nevertheless, to understand the long term consequences of neurotrauma, the extent of recovery in surgical sham may separately be quantified.