Crystallization test: A prognostic biomarker in oral potentially malignant disorders and oral cancer.

AIM: The aim of study is to evaluate the crystallization pattern seen in cupric chloride medium using haemolyzed blood of control, Oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC) patients. MATERIALS AND METHOD: Study comprise 90 patients including control, OPMDs and OSCC. To create a haemolysed blood, a drop of blood was obtained and distilled water was added. Crystallization test using 0.1 ml of haemolyzed blood and 20% of a 10 ml cupric chloride solution. During 24 to 28 hours, this solution was put in a BOD incubator. RESULT: Crystallization pattern in control group is eccentric placed nucleus and peripheral radiating lines while in OPMDs and OSCC presence of transverse bar. Crystallization test showed 100% positivity in OSCC while 73.33% seen in control group. 90% sensitivity in OSCC and 76.67% sensitivity in OPMDs. CONCLUSION: OPMDs lesion convert from white to mixed red and white lesion and OSCC appear as non-healing ulcer or ulcero-proliferative growth increase in number of transverse bars. More number of transverse bars suggestive of high malignant potential.

Alpha-cyperone mitigates renal ischemic injury via modulation of HDAC-2 expression in diabetes: Insights from molecular dynamics simulations and experimental evaluation.

Chronic diabetes mellitus is reported to be associated with acute kidney injury. The enzyme histone deacetylase-2 (HDAC-2) was found to be upregulated in diabetes-related kidney damage. Alpha-cyperone (α-CYP) is one of the active ingredients of Cyperus rotundus that possesses antioxidant and anti-inflammatory effects. We evaluated the effect of α-CYP on improving oxidative stress and tissue inflammation following renal ischemia/reperfusion (I/R) injury in diabetic rats. The effect of α-CYP on HDAC-2 expression in renal homogenates and in the NRK-52 E cell line was evaluated following renal I/R injury and high glucose conditions, respectively. Molecular docking was used to investigate the binding of α-CYP with the HDAC-2 active site. Both renal function and oxidative stress were shown to be impaired in diabetic rats due to renal I/R injury. Significant improvements in kidney/body weight ratio, creatinine clearance, serum creatinine, blood urea nitrogen (BUN), and uric acid were observed in diabetic rats treated with α-CYP (50 mg/kg) two weeks prior to renal I/R injury. α-CYP treatment also improved histological alterations in renal tissue and lowered levels of malondialdehyde, myeloperoxidase, and hydroxyproline. Treatment with α-CYP suppressed the increased HDAC-2 expression in the renal tissue of diabetic rats and in the NRK-52 E cell line. The molecular docking reveals that α-CYP binds to HDAC-2 with good affinity, ascertained by molecular dynamics simulations and binding free energy analysis. Overall, our data suggest that α-CYP can effectively prevent renal injury in diabetic rats by regulating oxidative stress, tissue inflammation, fibrosis and inhibiting HDAC-2 activity.

Androgen receptor: Structure, signaling, function and potential drug discovery biomarker in different breast cancer subtypes.

The Androgen Receptor (AR) is emerging as an important factor in the pathogenesis of breast cancer (BC), which is the most common malignancy worldwide. >70 % of AR expression in primary and metastatic breast tumors has been observed which suggests that AR may be a new marker and a potential therapeutic target among AR-positive BC patients. Biological insight into AR-positive breast cancer reveals that AR may cross-talk with several vital signaling pathways, including key molecules and receptors. Downstream signaling of AR might also affect many clinically important pathways that are emerging as clinical targets in BC. AR exhibits different behaviors depending on the breast cancer molecular subtype. Preliminary clinical research using AR-targeted drugs, which have already been FDA-approved for prostate cancer (PC), has given promising results for AR-positive breast cancer patients. However, since AR positivity's prognostic and predictive value remains uncertain, it is difficult to identify and stratify patients who would benefit from AR-targeted therapies alone. Thus, the need of the hour is to target the androgen receptor as a monotherapy or in combination with other conventional therapies which has proven to be an effective clinical strategy for the treatment of prostate cancer patients, and these therapeutic strategies are increasingly being investigated in breast cancer. Therefore, in this manuscript, we review the role of AR in various cellular processes that promote tumorigenesis and aggressiveness, in different subtypes of breast cancer, as well as discuss ongoing efforts to target AR for the more effective treatment and prevention of breast cancer.

The Yin and Yang of pathogens and probiotics: interplay between Salmonella enterica sv. Typhimurium and Bifidobacterium infantis during co-infection.

Probiotic bacteria have been proposed as an alternative to antibiotics for the control of antimicrobial resistant enteric pathogens. The mechanistic details of this approach remain unclear, in part because pathogen reduction appears to be both strain and ecology dependent. Here we tested the ability of five probiotic strains, including some from common probiotic genera Lactobacillus and Bifidobacterium, to reduce binding of Salmonella enterica sv. Typhimurium to epithelial cells in vitro. Bifidobacterium longum subsp. infantis emerged as a promising strain; however, S. Typhimurium infection outcome in epithelial cells was dependent on inoculation order, with B. infantis unable to rescue host cells from preceding or concurrent infection. We further investigated the complex mechanisms underlying this interaction between B. infantis, S. Typhimurium, and epithelial cells using a multi-omics approach that included gene expression and altered metabolism via metabolomics. Incubation with B. infantis repressed apoptotic pathways and induced anti-inflammatory cascades in epithelial cells. In contrast, co-incubation with B. infantis increased in S. Typhimurium the expression of virulence factors, induced anaerobic metabolism, and repressed components of arginine metabolism as well as altering the metabolic profile. Concurrent application of the probiotic and pathogen notably generated metabolic profiles more similar to that of the probiotic alone than to the pathogen, indicating a central role for metabolism in modulating probiotic-pathogen-host interactions. Together these data imply crosstalk via small molecules between the epithelial cells, pathogen and probiotic that consistently demonstrated unique molecular mechanisms specific probiotic/pathogen the individual associations.

Comparative evaluation of two different dental age estimation methods using tooth pulp: A CBCT study.

AIM: To estimate the age of an individual based on 3D radiographic evaluation of pulp width of maxillary central incisor. MATERIALS AND METHODS: This study included 185 CBCT images of individuals within age range of 14-64 years. Images were evaluated for maxillary central incisors and pulp width measurements were taken from cementoenamel junction and middle third of root. Obtained data was subjected to correlation and regression analysis from which the age of an individual was predicted. Results of the present study were compared with another study by the same authors. RESULTS: A negative linear relationship was obtained between age and pulp width. The standard error of estimate (SEE) in sagittal section was 11.36 years and that in coronal section was 11.23 years. The coefficient of determination for sagittal section was 0.107 and for coronal section was 0.127. An obtained regression formula was highly significant. Division of samples into various age groups reduced SEE drastically. CONCLUSION: It can be concluded that pulp width of maxillary central incisor is a reliable indicator of age estimation.

Neuroprotective effect of taxifolin against aluminum chloride-induced dementia and pathological alterations in the brain of rats: possible involvement of toll-like receptor 4.

Aluminum (Al) overexposure damages various organ systems, especially the nervous system. Regularly administered aluminum chloride (AlCl3) to rats causes dementia and pathophysiological alterations linked to Alzheimer's disease (AD). Taxifolin's neuroprotective effects against AlCl3-induced neurotoxicity in vitro and in vivo studies were studied. Taxifolin (0.1, 0.3, 1, 3, and 10 µM) was tested against AlCl3 (5 mM)-induced neurotoxicity in C6 and SH-SY5Y cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Additionally, neural morphology was examined by confocal microscopy. Additionally, taxifolin's mode of binding with the co-receptor of toll-like receptor 4 (TLR4), human myeloid differentiation-2 (hMD-2) was investigated. AlCl3 (25 mg/kg/d, i.p.) was administered to rats for 14 d, and from the eighth day, taxifolin (1, 2, and 5 mg/kg/d, i.p.) was given along with AlCl3. This study assessed memory impairment using the Morris water maze, plus maze, and pole tests. This study also performed measurement of oxidant (malondialdehyde [MDA] and nitrite), antioxidant (reduced glutathione), and inflammatory (myeloperoxidase [MPO] activity, TLR4 expression) parameters in rats' brain in addition to histopathology. The docking score for taxifolin with hMD-2 was found to be -4.38 kcal/mol. Taxifolin treatment reduced the neurotoxicity brought on by AlCl3 in both C6 and SH-SY5Y cells. Treatment with 10 µM taxifolin restored AlCl3-induced altered cell morphology. AlCl3 administration caused memory loss, oxidative stress, inflammation (increased MPO activity and TLR4 expression), and brain atrophy. Taxifolin treatment significantly improved the AlCl3-induced memory impairment. Taxifolin treatment also mitigated the histopathological and neurochemical consequences of repeated AlCl3 administration in rats. Thus, taxifolin may protect the brain against AD.

An update on new-age potential biomarkers for Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that deals with dopaminergic deficiency in Substantia nigra pars compact (SNpc) region of the brain. Dopaminergic deficiency manifests into motor dysfunction. Alpha-synuclein protein aggregation is the source for inception of the pathology. Motor symptoms include rigidity, akinesia, tremor and gait dysfunction. Pre-motor symptoms are also seen in early stage of the disease; however, they are not distinguishable. Lack of early diagnosis in PD pathology poses a major challenge for development of disease modifying therapeutics. Substantial neuronal loss has already been occurred before the clinical manifestations appear and hence, it becomes impossible to halt the disease progression. Current diagnostics are majorly based on the clinical symptoms and thus fail to detect early progression of the disease. Thus, there is need for early diagnosis of PD, for detection of the disease at its inception. This will facilitate the effective use of therapies that halt the progression and will make remission possible. Many novel biomarkers are being developed that include blood-based biomarker, CSF biomarker. Other than that, there are non-invasive techniques that can detect biomarkers. We aim to discuss potential role of these new age biomarkers and their association with PD pathogenesis in this review.

Localized delivery of Erlotinib using liposomal gel formulations for the treatment of oral squamous cell carcinoma.

Oral cancer accounts for more than 350,000 cases worldwide with 90% of them being oral squamous cell carcinomas (OSCC). The current treatment modalities of chemoradiation have poor outcomes along with harmful effects to neighbouring healthy tissues. The present study aimed to deliver Erlotinib (ERB), locally at the site of tumor arising in the oral cavity. ERB was encapsulated in liposomal formulations (ERB Lipo) and optimized using full factorial, 32 experimental design. The optimized batch was then coated with chitosan to obtain CS-ERB Lipo and were characterized further. Both liposomal ERB formulations had size <200 nm and PDI < 0.4. Zeta potential was upto -50 mV for ERB Lipo and upto +25 mV for CS-ERB Lipo indicating stable formulation. Liposomal formulations were freeze dried and loaded into gel to study in-vitro release and chemotherapeutic evaluation. CS-ERB Lipo showed sustained release upto 36 h from gel as compared to control formulation. In-vitro cell viability studies showed potent anti-cancer activity on KB-cells. In-vivo studies showed better pharmacological efficacy in terms of tumor volume reduction for ERB Lipo gel (49.19%) and CS-ERB Lipo gel (55.27%) as compared to plain ERB Gel (38.88%) applied locally. Histology also revealed that formulation could alleviate dysplasia condition to hyperplasia. The locoregional therapy of ERB Lipo gel and CS-ERB Lipo gel thus show promising outcome in improving pre-malignant and early-stage oral cavity cancers.

Uncovering Novel Therapeutic Targets for Parkinson's Disease.

Parkinson's disease (PD) is the second most prevailing progressive disorder leading to neurodegeneration, typically in people above 65 years of age. Motor clinical manifestations of PD appear in a much later stage and include rigidity, tremors, akinesia, and gait dysfunction. There are also nonmotor symptoms like GI and olfactory dysfunction. However, they cannot be considered for diagnosis of the disease, as they are unspecific. PD pathogenesis is mainly characterized by deposits of inclusion bodies on dopaminergic (DA) neurons in substantia nigra pars compacta region (SNpc) of the brain. The major component of these inclusion bodies, are α-synuclein aggregates. α-Synuclein undergoes misfolding and oligomerization to form aggregates and fibrils. These aggregates gradually propagate PD pathology. Other prominent features of this pathological development include mitochondrial dysfunction, neuroinflammation, oxidative stress, and impaired autophagy. These all contribute to neuronal degeneration. Besides this, there are many underlying factors which influence these processes. These factors comprise molecular proteins and signaling cascades. In this review, we have listed out underexplored molecular targets that may aid in development of neoteric and advanced therapeutics.

Salmonella enhances osteogenic differentiation in adipose-derived mesenchymal stem cells.

The potential of mesenchymal stem cells (MSCs) for tissue repair and regeneration has garnered great attention. While MSCs are likely to interact with microbes at sites of tissue damage and inflammation, like in the gastrointestinal system, the consequences of pathogenic association on MSC activities have yet to be elucidated. This study investigated the effects of pathogenic interaction on MSC trilineage differentiation paths and mechanisms using model intracellular pathogen Salmonella enterica ssp enterica serotype Typhimurium. The examination of key markers of differentiation, apoptosis, and immunomodulation demonstrated that Salmonella altered osteogenic and chondrogenic differentiation pathways in human and goat adipose-derived MSCs. Anti-apoptotic and pro-proliferative responses were also significantly upregulated (p < 0.05) in MSCs during Salmonella challenge. These results together indicate that Salmonella, and potentially other pathogenic bacteria, can induce pathways that influence both apoptotic response and functional differentiation trajectories in MSCs, highlighting that microbes have a potentially significant role as influencers of MSC physiology and immune activity.

Celastrus paniculatus oil ameliorates NF-KB mediated neuroinflammation and synaptic plasticity in the scopolamine-induced cognitive impairment rat model.

BACKGROUND AND AIM: Traditionally, Celastrus paniculatus Willd. (CP) oil has been utilized as a tranquilizer and memory enhancer. The present study investigated the neuropharmacological activity and efficacy of CP oil in ameliorating scopolamine-induced cognitive impairment in rats. EXPERIMENTAL PROCEDURE: Cognitive deficiency was induced in rats by administration of scopolamine (2 mg/kg intraperitoneal injection) for a period of 15 days. Donepezil served as a reference drug and CP oil was tested as both preventive and curative treatments. Animals' behaviour was assessed through the Morris water maze (MWM), novel object preference (NOR), and conditioned avoidance (CA) tests. Oxidative stress parameters, bioamine concentration (dopamine, noradrenaline, and 5-hydroxytryptamine), nerve growth factor (NGF), interleukin-6 (IL-6), nuclear factor kappa B (NF-кB), and tumor necrosis factor-alpha (TNFα) were estimated. Synaptophysin immunohistochemistry was performed. RESULTS: Our results showed that CP oil ameliorated behavioural deficits. It reduced latency to find a hidden platform in MWM. Reduced novel object exploration time and discrimination index (p < 0.05) in the NOR. Reduced step-down latency and normalized conditioned avoidance response (p < 0.001) in the CA test. CP oil increased dopamine, serotonin, norepinephrine, superoxide dismutase (SOD), glutathione, and catalase levels. It decreased malondialdehyde (MDA), acetylcholinesterase activity, IL-6, NF-кB (P < 0.001), TNFα, and NGF levels. Treatment showed approximate typical reactivity to synaptophysin. CONCLUSION: Our data is suggestive that CP oil treatment improves behavioural test outcomes, increases biogenic amine concentration, and decreases acetylcholinesterase activity, and neuroinflammatory biomarkers. It also restores synaptic plasticity. It thus improves cognitive functions against scopolamine-induced amnesia in rats by improving cholinergic function.

Beneficial effects of buspirone in endothelin-1 induced stroke cachexia in rats.

Stroke cachexia is associated with prolonged inflammation, muscle loss, poor prognosis, and early death of stroke patients. No particular treatment is available to cure the symptoms or disease. The present study aimed to evaluate the effect of a 5-HT1a agonist, buspirone on stroke cachexia. Wistar rats were injected with endothelin-1 to the bregma region of the brain to induce ischemic stroke followed by induction of cachexia after 4 days. Treatment with buspirone (3 mg/kg p.o) was given for 4 weeks after confirmation of cachexia in animals. Disease control animals exhibited decrease in wire hanging time and increase in foot fault numbers compared to normal animals. Disease control animals also showed weight loss, decrease in food intake, increased serum glucose and lipid profile along with high serum levels of inflammatory cytokines-TNF-α, IL-6 and decrease in weight of skeletal muscle and adipose tissues. Treatment with buspirone improves behavioural parameters along with increases food intake and body weight, decreased inflammatory cytokines IL-6 and TNF-α and serum glucose levels with increase in lipid profile. Buspirone also increased the weight of adipose tissue and maintain the skeletal muscle architecture and function as depicted in histopathological studies. Our study suggests that buspirone produces beneficial role in stroke cachexia by increasing body weight, food intake and adipose tissue depots by activating on 5-HT receptors. Buspirone decreases inflammatory markers in stroke cachexia although mechanism behind it was not fully understood. Buspirone decreases circulating blood glucose by stimulating glucose uptake in skeletal muscle via 5-HT receptors and maintained lipid profile. Buspirone was found to be effective in ameliorating cachectic conditions in stroke.

Prevalence and factors associated with oral potentially malignant disorders and oral squamous cell carcinoma: An institutional study.

INTRODUCTION: Incidence & prevalence of OPMDs & OSCC is increasing day by day, thereby escalating the burden of oral cancer in India. Oral cancer ranks in the top three of all cancers in India and is quickly becoming a health priority. This study aims to assess prevalence and associated factors of OPMDs and OSCC in patients attending dental OPD and its association with age, gender, habit (type & duration), clinical presentation and site of involvement. MATERIAL AND METHODS: A prospectively 12 months study was conducted in the outpatient department. Patient's data whether suspected or proven cases of OPMDs & OSCC and fits in clinical criteria were reviewed and analysed for demographic data, oral adverse habit, clinical presentation and site of involvement. RESULTS: Overall 38,588 patient's data were analysed for 12 month time duration. Out of this 552 (1.43%) cases of OPMDs and 58 (0.15%) cases of OSCC were reported. Out of 552 maximum patients were reported with OSMF (34.4%), followed by other lesions and minimum with LP (7.9%). Age group most commonly affected was above 45 years (44.9%) of age. Males (81.1%) were affected more than females. OPMDs (92%) and OSCC (96.5%) were mostly associated with smokeless or smoking form of tobacco. CONCLUSION: Present study evaluated the prevalence rates and associated factors of OPMDs & OSCC, which is beneficial for general practitioner in early diagnosis, formulating better treatment plan and to educate general population about risk factors, early signs and symptoms of these lesions.

Antitumor effects of polyphenol-rich extract of Euphoria longana seed by vascular endothelial growth factor and transforming growth factor-beta signaling inhibition in experimentally induced oral cancer in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Oral cancers are found to have high risk in South Central Asia due to exposure of various risk factors. Euphoria longana Lam. (EL) has been traditionally used to relieve insomnia, prevent amnesia, and treat palpitation. In addition, EL has been reported to have anti-inflammatory, anti-cancer, and antioxidant activities. The investigation was aimed to evaluate the mechanism of action and antitumor activity of polyphenol-rich EL seeds extract against oral cancer induced by 4-Nitroquinoline-1-oxide (4-NQO). MATERIALS AND METHODS: Seven groups of Sprague-Dawley rats were formulated: normal animals, oral cancer induced with 4-NQO, EL-treated normal control, EL-treated disease control from 0-day, EL-treated disease control from 60 days, 5-fluorouracil (5-FU)-treated disease control from day 60, and combined EL- and 5-FU-treated disease control animals from day 60. The animal tongue was smeared with 0.5% 4-NQO at frequency of thrice a week for 12 weeks to induce oral cancer. At the end of treatment, excised tongues were used for biochemical and tumour-specific parameters along with histopathology assessment. RESULTS: Treatment with EL, 5-FU, and combination of both in diseased animals exhibited significant improvement in interleukin-6, vascular endothelial growth factor (VEGF), and Transforming growth factor beta (TGF-ß) levels, antioxidant status together with histoarchitecture of the tongue tissue. In addition, the combination of both was slightly more effective than EL and 5-FU alone. CONCLUSION: Our data suggest antitumor activity of Euphoria longana Lam. Extract against 4-NQO induced oral cancer in rats, which could be attributed to alteration in the VEGF and TGF-ß signaling axis.

TGF-ß at the crossroads of multiple prognosis in breast cancer, and beyond.

Transforming growth factor ß (TGF-ß), a pluripotent cytokine and a multifunctional growth factor has a crucial role in varied biological mechanisms like invasion, migration, epithelial-mesenchymal transition, apoptosis, wound healing, and immunosuppression. Moreover, it also has an imperative role both in normal mammary gland development as well as breast carcinogenesis. TGF-ß has shown to have a paradoxical role in breast carcinogenesis, by transitioning from a growth inhibitor to a growth promoter with the disease advancement. The inter-communication and crosstalk of TGF-ß with different signaling pathways has strengthened the likelihood to explore it as a comprehensive biomarker. In the last two decades, TGF-ß has been studied extensively and has been found to be a promising biomarker for early detection, disease monitoring, treatment selection, and tumor progression making it beneficial for disease management. In this review, we focus on the signaling pathways and biological activities of the TGF-ß family in breast cancer pathogenesis and its role as a circulatory and independent biomarker for breast cancer progression and metastasis. Moreover, this review highlights TGF-ß as a drug target, and the underlying mechanisms through which it is involved in tumorigenesis that will aid in the development of varied therapies targeting the different stages of breast cancer.

Vitamin D3 supplementation ameliorates cognitive impairment and alters neurodegenerative and inflammatory markers in scopolamine induced rat model.

A multifaceted approach can be effective for the treatment of dementia including the most common form, Alzheimer's disease (AD). However, currently, it involves only symptomatic treatment with cholinergic drugs. Beneficial effects of high Vitamin D3 levels or its intake in the prevention and treatment of cognitive disorders have been reported. Thus, the present study examined the preventive effect of Vitamin D3 (Calcitriol) supplementation on cognitive impairment and evaluated its impact on the accumulation or degradation of Aß plaques. A single intraperitoneal injection of scopolamine was used to induce cognitive impairment in rats. Treatment of Vitamin D3 was provided for 21 days after the injection. Various behavioral parameters like learning, spatial memory and exploratory behavior, biochemical alterations in the brain homogenate and histology of the hippocampus were investigated. Our results indicated that scopolamine-induced rats depicted cognitive deficits with high Aß levels and hyperphosphorylated tau proteins in the brain tissue, while Vitamin D supplementation could significantly improve the cognitive status and lower these protein levels. These results were supported by the histopathological and immunohistochemical staining of the hippocampal brain region. Furthermore, mechanistic analysis depicted that Vitamin D supplementation improved the Aß protein clearance by increasing the neprilysin levels. It also reduced the accumulation of Aß plaques by lowering neuroinflammation as well as oxidative stress. The present findings indicate that Vitamin D3 supplementation can ameliorate cognitive deficits and thereby delay AD progression by increasing Aß plaque degradation, reducing inflammation and oxidative stress.

Insights of Valacyclovir in Treatment of Alzheimer's Disease: Computational Docking Studies and Scopolamine Rat Model.

BACKGROUND: Alzheimer's Disease (AD) impairs memory and cognitive functions in the geriatric population and is characterized by intracellular deposition of neurofibrillary tangles, extracellular deposition of amyloid plaques, and neuronal degeneration. Literature suggests that latent viral infections in the brain act as prions and promote neurodegeneration. Memantine possesses both anti-viral and N-methyl-D-aspartate (NMDA) receptor antagonistic activity. OBJECTIVES: This research was designed to evaluate the efficacy of antiviral agents, especially valacyclovir, a prodrug of acyclovir in ameliorating the pathology of AD based on the presumption that anti-viral agents targeting the Herpes Simplex Virus (HSV) can have a protective effect on neurodegenerative diseases like Alzheimer's disease. METHODS: Thus, we evaluated acyclovir's potential activity by in-silico computational docking studies against acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase 1 (BACE-1). These findings were further evaluated by in-vivo scopolamine-induced cognitive impairment in rats. Two doses of valacyclovir, a prodrug of acyclovir (100 mg/kg and 150 mg/kg orally) were tested. RESULTS: Genetic Optimisation for Ligand Docking scores and fitness scores of acyclovir were comparable to donepezil. Valacyclovir improved neurobehavioral markers. It inhibited AChE and BuChE (p<0.001) enzymes. It also possessed disease-modifying efficacy as it decreased the levels of BACE-1 (p<0.001), amyloid beta 1-42 (p<0.001), amyloid beta 1-40 (p<0.001), phosphorylatedtau (p<0.001), neprilysin (p<0.01), and insulin-degrading enzyme. It ameliorated neuroinflammation through decreased levels of tumour necrosis factor α (p<0.001), nuclear factor-kappa B (p<0.001), interleukin 6 (p<0.001), interleukin 1 beta (p<0.001), and interferon-gamma (p<0.001). It also maintained synaptic plasticity and consolidated memory. Histopathology showed that valacyclovir could restore cellular density and also preserve the dentate gyrus. CONCLUSION: Valacyclovir showed comparable activity to donepezil and thus can be further researched for the treatment of Alzheimer's disease.

Lipoid proteinosis: Review of Indian cases.

Lipoid proteinosis (LP) is a rare autosomal recessive disorder characterized by the deposition of amorphous hyaline material in the dermis and submucosal connective tissue. To date <500 cases of LP have been described and oral manifestations described in a very few reports. Indian cases are much less reported and reviewed. Hence, here review of 51 Indian LP cases along with a case of histologically proven LP in 12-year-old male patient with typical skin, ocular, laryngeal, oral and radiographic features is done. Cases from 1969 to 2021 were collected using keyword LP on google and google scholar and Indian cases were analyzed afterward. Review with case presentation regarding oral manifestations will help the oral physician to diagnose LP in early stage.

Alzheimer's disease: a scoping review of biomarker research and development for effective disease diagnosis.

INTRODUCTION: Alzheimer's disease (AD) is regarded as the foremost reason for neurodegeneration that prominently affects the geriatric population. Characterized by extracellular accumulation of amyloid-beta (Aß), intracellular aggregation of hyperphosphorylated tau (p-tau), and neuronal degeneration that causes impairment of memory and cognition. Amyloid/tau/neurodegeneration (ATN) classification is utilized for research purposes and involves amyloid, tau, and neuronal injury staging through MRI, PET scanning, and CSF protein concentration estimations. CSF sampling is invasive, and MRI and PET scanning requires sophisticated radiological facilities which limit its widespread diagnostic use. ATN classification lacks effectiveness in preclinical AD. AREAS COVERED: This publication intends to collate and review the existing biomarker profile and the current research and development of a new arsenal of biomarkers for AD pathology from different biological samples, microRNA (miRNA), proteomics, metabolomics, artificial intelligence, and machine learning for AD screening, diagnosis, prognosis, and monitoring of AD treatments. EXPERT OPINION: It is an accepted observation that AD-related pathological changes occur over a long period of time before the first symptoms are observed providing ample opportunity for detection of biological alterations in various biological samples that can aid in early diagnosis and modify treatment outcomes.