Recent Advances in Genomic Studies of Gestational Duration and Preterm Birth.

Preterm birth (PTB) is the leading cause of infant mortality and morbidity. For several decades, extensive epidemiologic and genetic studies have highlighted the significant contribution of maternal and offspring genetic factors to PTB. This review discusses the challenges inherent in conventional genomic analyses of PTB and underscores the importance of adopting nonconventional approaches, such as analyzing the mother-child pair as a single analytical unit, to disentangle the intertwined maternal and fetal genetic influences. We elaborate on studies investigating PTB phenotypes through 3 levels of genetic analyses: single-variant, multi-variant, and genome-wide variants.

Most recent advances and applications of extracellular vesicles in tackling neurological challenges.

Over the past few decades, there has been a notable increase in the global burden of central nervous system (CNS) diseases. Despite advances in technology and therapeutic options, neurological and neurodegenerative disorders persist as significant challenges in treatment and cure. Recently, there has been a remarkable surge of interest in extracellular vesicles (EVs) as pivotal mediators of intercellular communication. As carriers of molecular cargo, EVs demonstrate the ability to traverse the blood-brain barrier, enabling bidirectional communication. As a result, they have garnered attention as potential biomarkers and therapeutic agents, whether in their natural form or after being engineered for use in the CNS. This review article aims to provide a comprehensive introduction to EVs, encompassing various aspects such as their diverse isolation methods, characterization, handling, storage, and different routes for EV administration. Additionally, it underscores the recent advances in their potential applications in neurodegenerative disorder therapeutics. By exploring their unique capabilities, this study sheds light on the promising future of EVs in clinical research. It considers the inherent challenges and limitations of these emerging applications while incorporating the most recent updates in the field.

PET imaging of microglia using PBR28suv determines therapeutic efficacy of autologous bone marrow mononuclear cells therapy in traumatic brain injury.

Traumatic brain injury (TBI) results in activated microglia. Activated microglia can be measured in vivo by using positron emission topography (PET) ligand peripheral benzodiazepine receptor standardized uptake values (PBR28suv). Cell based therapies have utilized autologous bone marrow mononuclear cells (BMMNCs) to attenuate activated microglia after TBI. This study aims to utilize in vivo PBR28suv to assess the efficacy of BMMNCs therapy after TBI. Seventy-two hours after CCI injury, BMMNCs were harvested from the tibia and injected via tail-vein at 74 h after injury at a concentration of 2 million cells per kilogram of body weight. There were three groups of rats: Sham, CCI-alone and CCI-BMMNCs (AUTO). One hundred twenty days after injury, rodents were imaged with PBR28 and their cognitive behavior assessed utilizing the Morris Water Maze. Subsequent ex vivo analysis included brain volume and immunohistochemistry. BMMNCs therapy attenuated PBR28suv in comparison to CCI alone and it improved spatial learning as measured by the Morris Water Maze. Ex vivo analysis demonstrated preservation of brain volume, a decrease in amoeboid-shaped microglia in the dentate gyrus and an increase in the ratio of ramified to amoeboid microglia in the thalamus. PBR28suv is a viable option to measure efficacy of BMMNCs therapy after TBI.

A substrate for a cell free in vitro assay system to screen drugs targeting trypsin like protease-based cleavage of SARS-CoV-2 spike glycoprotein and viral entry.

Host proteases trypsin and trypsin-like proteases have been reported to facilitate the entry of coronavirus SARS-CoV-2 in its host cells. These protease enzymes cleave the viral surface glycoprotein, spike, leading to successful cell surface receptor attachment, fusion and entry of the virus in its host cell. The spike protein has protease cleavage sites between the two domains S1 and S2. Since the cleavage site is recognized by the host proteases, it can be a potential antiviral therapeutic target. Trypsin-like proteases play an important role in virus infectivity and the property of spike protein cleavage by trypsin and trypsin-like proteases can be used to design assays for screening of antiviral candidates against spike protein cleavage. Here, we have documented the development of a proof-of-concept assay system for screening drugs against trypsin/trypsin-like proteases that cleave spike protein between its S1 and S2 domains. The assay system developed uses a fusion substrate protein containing a NanoLuc luciferase reporter protein, the protease cleavage site between S1 and S2 domains of SARS-CoV-2 spike protein and a cellulose binding domain. The substrate protein can be immobilized on cellulose via the cellulose binding domain of the substrate. When trypsin and trypsin-like proteases cleave the substrate, the cellulose binding domain remain bound to the cellulose and the reporter protein is dislodged. Reporter assay using the released reporter protein is the read out of the protease activity. We have demonstrated the proof-of-concept using multiple proteases like trypsin, TMPRSS2, furin, cathepsin B, human airway trypsin and cathepsin L. A significant increment in fold change was observed with increasing enzyme concentration and incubation time. Introduction of increasing amounts of enzyme inhibitors in the reaction reduced the luminescent signal, thus validating the assay. Furthermore, we used SDS-PAGE and immunoblot analyses to study the cleavage band pattern and re-confirm the cleavage for enzymes tested in the assay. Taken together, we have tested an in-vitro assay system using the proposed substrate for screening drugs against trypsin like protease-based cleavage of SARS-CoV-2 spike glycoprotein. The assay system can also be potentially used for antiviral drug screening against any other enzyme that might cleave the used cleavage site.

Heritability Estimation Approaches Utilizing Genome-Wide Data.

Prior to the development of genome-wide arrays and whole genome sequencing technologies, heritability estimation mainly relied on the study of related individuals. Over the past decade, various approaches have been developed to estimate SNP-based narrow-sense heritability ( h SNP 2 ${\rm{h}}_{{\rm{SNP}}}^2$ ) in unrelated individuals. These latter approaches use either individual-level genetic variations or summary results from genome-wide association studies (GWAS). Recently, several studies compared these approaches using extensive simulations and empirical datasets. However, sparse information on hands-on training necessitates revisiting these approaches from the perspective of a stepwise guide for practical applications. Here, we provide an overview of the commonly used SNP-heritability estimation approaches utilizing genome-wide array, imputed or whole genome data from unrelated individuals, or summary results. We not only discuss these approaches based on their statistical concepts, utility, advantages, and limitations, but also provide step-by-step protocols to apply these approaches. For illustration purposes, we estimate h SNP 2 ${\rm{h}}_{{\rm{SNP}}}^2$ of height and BMI utilizing individual-level data from The Northern Finland Birth Cohort (NFBC) and summary results from the Genetic Investigation of ANthropometric Traits (GIANT;) consortium. We present this review as a template for the researchers who estimate and use heritability in their studies and as a reference for geneticists who develop or extend heritability estimation approaches. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: GREML (GCTA) Alternate Protocol 1: Stratified GREML Basic Protocol 2: LDAK Alternate Protocol 2: Stratified LDAK Basic Protocol 3: Threshold GREML Basic Protocol 4: LD score (LDSC) regression Basic Protocol 5: SumHer.

How Does the Public Evaluate Vaccines for Low-Incidence, Severe-Outcome Diseases? A General-Population Choice Experiment.

BACKGROUND: Because immunizing large numbers of healthy people could be required to reduce a relatively small number of infections, disease incidence has a large impact on cost effectiveness, even if the infection is associated with very serious health outcomes. In addition to cost effectiveness, the US Advisory Committee on Immunization Practices requires evidence of stakeholders' values and preferences to help inform vaccine recommendations. This study quantified general-population preferences for vaccine trade-offs among disease severity, disease incidence, and other vaccine features. METHODS: We developed a best-practice discrete choice experiment survey and administered it to 1185 parents of children aged 12-23 years and 1203 young adults aged 18-25 years from a national opt-in consumer panel. The data were analyzed using exploded-logit latent-class analysis. RESULTS: Latent-class analysis identified two classes with similar relative-importance weights in both samples. One of the two classes represented about half the samples and had preferences consistent with well-structured, logically ordered, and acceptably precise stated-preference utility. Preferences for the other half of the samples were poorly defined over the ranges of vaccine and disease attributes evaluated. Both parents and young adults in the first class evaluated protection from a disease with 1 in 100 incidence and full recovery at home as having statistically the same preference utility as a disease with 1 in 1 million incidence requiring hospitalization and resulting in permanent deafness. CONCLUSIONS: The results suggest that vaccines that protect against low-incidence, severe-outcome diseases, provide 'peace of mind' benefits not captured by standard health-outcome metrics. The fact that half the respondents had poorly defined vaccine preferences is a reminder of the challenges of implementing patient-centric vaccine decision making.

Complexity of Tumor Microenvironment: Therapeutic Role of Curcumin and Its Metabolites.

The tumor microenvironment (TME) is a complex network of cellular and non-cellular components surrounding the tumor. The cellular component includes fibroblasts, adipocytes, endothelial cells, and immune cells, while non-cellular components are tumor vasculature, extracellular matrix and signaling molecules. The tumor cells have constant close interaction with their surrounding TME components that facilitate their growth, survival, and metastasis. Targeting a complex TME network and its interaction with the tumor can offer a novel strategy to disrupt cancer cell progression. Curcumin, from turmeric rhizome, is recognized as a safe and effective natural therapeutic agent against multiple diseases including cancer. Here the effects of curcumin and its metabolites on tumor-TME interaction modulating ability have been described. Curcumin and its metabolites regulate TME by inhibiting the growth of its cellular components such as cancer-associated adipocytes, cancer-associated fibroblast, tumor endothelial cells, tumor-stimulating immune cells, and inducing anticancer immune cells. They also inhibit the interplay of tumor cells to TME by suppressing non-cellular components such as extracellular matrix, and associated tumor promoting signaling-pathways. In addition, curcumin inhibits the inflammatory environment, suppresses angiogenic factors, and increases antioxidant status in TME. Overall, curcumin has the capability to regulate TME components and their interaction with tumor cells.

Using Sentinel-1, Sentinel-2, and Planet satellite data to map field-level tillage practices in smallholder systems.

Remote sensing can be used to map tillage practices at large spatial and temporal scales. However, detecting such management practices in smallholder systems is challenging given that the size of fields is smaller than historical readily-available satellite imagery. In this study we used newer, higher-resolution satellite data from Sentinel-1, Sentinel-2, and Planet to map tillage practices in the Eastern Indo-Gangetic Plains in India. We specifically tested the classification performance of single sensor and multiple sensor random forest models, and the impact of spatial, temporal, or spectral resolution on classification accuracy. We found that when considering a single sensor, the model that used Planet imagery (3 m) had the highest classification accuracy (86.55%) while the model that used Sentinel-1 data (10 m) had the lowest classification accuracy (62.28%). When considering sensor combinations, the model that used data from all three sensors achieved the highest classification accuracy (87.71%), though this model was not statistically different from the Planet only model when considering 95% confidence intervals from bootstrap analyses. We also found that high levels of accuracy could be achieved by only using imagery from the sowing period. Considering the impact of spatial, temporal, and spectral resolution on classification accuracy, we found that improved spatial resolution from Planet contributed the most to improved classification accuracy. Overall, it is possible to use readily-available, high spatial resolution satellite data to map tillage practices of smallholder farms, even in heterogeneous systems with small field sizes.

Apoptosis signal-regulating kinase-1 regulates thrombin-induced endothelial permeability.

Thrombin-induced endothelial permeability is associated with various pathological conditions. Apoptosis signal-regulating kinase-1 (ASK1), one of the upstream MAP3K, has been reported to be an important regulator of endothelial stress and apoptosis. Despite this, its role in endothelial permeability is unknown. The aim of this study was to determine the role of ASK1 in thrombin-induced endothelial permeability. To do so, a live cell monitoring system and transwell assay were used to evaluate in vitro endothelial permeability, while a Miles assay was used for in vivo permeability. Immunofluorescence and western blotting were used to visualize integrity of the junctions and phosphorylation of various proteins, respectively. We observed that in vivo thrombin-induced vascular permeability was attenuated in Ask1-/- mice. Pretreatment of human primary endothelial cells (ECs) with GS-4997 (ASK1 inhibitor) and deficiency of ASK1 in primary mouse lung ECs significantly attenuated the thrombin-induced endothelial permeability. Furthermore, in the presence of GS-4997, the following were also significantly reduced: thrombin-induced para-cellular gap formation, VE-cadherin proteolysis, and dislocation of VE-cadherin, JAM-A, and ZO1 from the junctions. Inhibition of ASK1 restored peripheral location of F-actin, similar to that induced by sphingosine-1-phosphate. These results suggest a unique role for ASK1 in regulating thrombin-induced endothelial permeability.

Role of Extracellular Vesicles in Glia-Neuron Intercellular Communication.

Cross talk between glia and neurons is crucial for a variety of biological functions, ranging from nervous system development, axonal conduction, synaptic transmission, neural circuit maturation, to homeostasis maintenance. Extracellular vesicles (EVs), which were initially described as cellular debris and were devoid of biological function, are now recognized as key components in cell-cell communication and play a critical role in glia-neuron communication. EVs transport the proteins, lipids, and nucleic acid cargo in intercellular communication, which alters target cells structurally and functionally. A better understanding of the roles of EVs in glia-neuron communication, both in physiological and pathological conditions, can aid in the discovery of novel therapeutic targets and the development of new biomarkers. This review aims to demonstrate that different types of glia and neuronal cells secrete various types of EVs, resulting in specific functions in intercellular communications.

Anti-viral triterpenes: a review.

Triterpenes are naturally occurring derivatives biosynthesized following the isoprene rule of Ruzicka. The triterpenes have been reported to possess a wide range of therapeutic applications including anti-viral properties. In this review, the recent studies (2010-2020) concerning the anti-viral activities of triterpenes have been summarized. The structure activity relationship studies have been described as well as brief biosynthesis of these triterpenes is discussed.

KLF8 is activated by TGF-ß1 via Smad2 and contributes to ovarian cancer progression.

Krüppel-like factor 8 (KLF8) is a transcription factor expressed abnormally in various cancer types and promotes oncogenic transformation. However, the role of KLF8 in ovarian cancer (OC) progression remains unclear. This study reports that transforming growth factor-ß1 (TGF-ß1)/Smad2/KLF8 axis regulates epithelial-mesenchymal transition (EMT) and contributes to OC progression. We analyzed the KLF8 expression in OC cells and tissues, wherein a significant overexpression of KLF8 was observed. Increased KLF8 expressions were correlated with higher cell proliferation, EMT, migration, and invasion and conferred poor clinical outcomes in OC patients. Overexpressed KLF8 increases F-actin polymerization and induces cytoskeleton remodeling of OC cells. Furthermore, a dissection of the molecular mechanism defined that TGF-ß1 triggers KLF8 through the Smad2 pathway and regulates EMT. Pharmacological and genetic inhibition of Smad2 followed by TGF-ß1 treatment failed to activate KLF8 expression and induction of EMT. Using promoter-luciferase reporter assays, we defined that upon TGF-ß1 activation, phosphorylated Smad2 binds and promotes the KLF8 promoter activity, and knockdown of Smad2 inhibits KLF8 promoter activation. Together, these results demonstrate that TGF-ß1 activates KLF8 expression by the Smad2 pathway, and KLF8 contributes to OC progression and may serve as a potential therapeutic strategy for treating OC patients.

Making a Shared Decision on Meningococcal B Vaccine: Provider Feedback on an Educational Tool Developed for Use With Patients.

BACKGROUND: In 2015, the Advisory Committee on Immunization Practices recommended Meningococcal B vaccination for healthy 16- to 23-year-olds based on shared clinical decision-making between the patient and the provider. There has been some confusion regarding how to implement this recommendation. METHODS: Through discussions among the authors, a review of relevant literature, and consultation with vaccine experts, we developed educational materials for providers that included a patient handout to help initiate and guide conversations leading to shared clinical decision-making for the Meningococcal B vaccine. Materials were distributed to 88 health care providers who subsequently completed surveys to evaluate their impressions of the materials and the utility of the materials for clinical practice. RESULTS: The survey results from the 88 providers revealed that they valued the materials; 93% percent indicated they would share these materials with colleagues, and 95% agreed or strongly agreed that they would share these materials with patient families. Responses to an open-ended question indicate that some providers initiated discussions regarding the Meningococcal B vaccine in ways that truncated conversation rather than encouraging a shared decision-making process. CONCLUSIONS: Overall, the materials developed and implemented for this project support the initiation of, and help standardize provider conversations regarding, Meningococcal B vaccination for healthy adolescents.

Purification and identification of anticancer organosulfides from Ferula assa-foetida gum: integrative analysis employing GC/GC-MS/RP-HPLC/NMR.

Ferula assa-foetida, containing organosulfides is widely used in Indian cuisine and traditionally claimed to have several medicinal properties including anticancer properties. Ferula oil enriched with organosulfides displayed significant inhibition of the cell growth in-vitro against SKOV3 and A549 cancer cells in a dose-dependent manner. This prompted us to investigate and delineate the compounds responsible for the activity. In this endeavor, the employed GC/GC-MS analysis resulted in the indecisive outcome. This led to the development of an expedient isocratic RP-HPLC method for the separation and purification of four major compounds which were further unambiguously characterised as (-)-E-2-butyl propenyl disulfide, (-)-Z-2-butyl propenyl disulfide, (-)-1-(methylthio)propyl(E)-1-propenyl disulfide, and (-)-1-(methylthio)propyl(Z)-1-propenyl disulfide employing 1H, 13C, and 2 D NMR. The isolated compounds were further evaluated for their potential against SKOV3 and A549 cell lines where a trisulfide has displayed better activity.

Land gradient and configuration effects on yield, irrigation amount and irrigation water productivity in rice-wheat and maize-wheat cropping systems in Eastern India.

Laser land levelling is expanding rapidly in the rice-wheat (RW) and maize-wheat (MW) systems of the Indo-Gangetic Plains of India and Pakistan. Current practice is to level to zero (0%) gradient, whereas a small gradient (e.g. 0.1%) is typically used in developed countries. Therefore, experiments were conducted in farmers' plots (~15 m x 40 m) in the Eastern Gangetic Plains to evaluate laser levelling with a 0.1% gradient in comparison with 0% and farmer levelling practice (FL). The study was conducted over two years in RW and MW systems. In the MW system, raised beds in plots lasered with 0% and 0.1% gradients were also evaluated. Laser levelling with 0% gradient significantly reduced irrigation amount and/or increased irrigation water productivity (WPi) in all crops/systems grown on the flat compared to FL except for wheat in the MW system. While there was a consistent trend for higher yield with a 0% gradient compared with FL, the differences were not significant in any crop/system. For the RW system, the results suggest no to marginal benefits in irrigation amount and WPi from levelling with a 0.1% gradient in comparison with 0% gradient. In that system, by far the bigger gains were from changing from FL to laser levelling with 0% gradient. This resulted in substantial reductions in irrigation amount, which greatly increased WPi in both crops (by ~40%), while yield was not affected. Rice grown with FL was not profitable, but lasering with 0% gradient significantly increased gross margin for rice, wheat and the total RW system. As for the RW system, levelling to 0% with a flat configuration significantly increased WPi of both crops in the MW system compared to FL, but by a lesser proportion. Raised beds significantly increased yield of maize by 8% (0.5 t ha-1), reduced irrigation amount by 20% (40 mm) and increased WPi by 34% (1.0 kg m-3) in comparison with the laser levelled flat plots. Gross margin of the MW system on beds was 17-20% higher than FL, and gross margin with beds on a 0.1% gradient was significantly higher than either gradient on the flat. The results suggest that the gains from levelling with a 0.1% gradient compared to 0% are marginal; however, this may change if the goal of consolidation of small farmer plots into larger fields becomes a reality provided there is a proportionate increase in irrigation flow rates, and ability to drain.

Genetic variations influence brain changes in patients with attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is a neurological and neurodevelopmental childhood-onset disorder characterized by a persistent pattern of inattentiveness, impulsiveness, restlessness, and hyperactivity. These symptoms may continue in 55-66% of cases from childhood into adulthood. Even though the precise etiology of ADHD is not fully understood, it is considered as a multifactorial and heterogeneous disorder with several contributing factors such as heritability, auxiliary to neurodevelopmental issues, severe brain injuries, neuroinflammation, consanguineous marriages, premature birth, and exposure to environmental toxins. Neuroimaging and neurodevelopmental assessments may help to explore the possible role of genetic variations on ADHD neuropsychobiology. Multiple genetic studies have observed a strong genetic association with various aspects of neuropsychobiological functions, including neural abnormalities and delayed neurodevelopment in ADHD. The advancement in neuroimaging and molecular genomics offers the opportunity to analyze the impact of genetic variations alongside its dysregulated pathways on structural and functional derived brain imaging phenotypes in various neurological and psychiatric disorders, including ADHD. Recently, neuroimaging genomic studies observed a significant association of brain imaging phenotypes with genetic susceptibility in ADHD. Integrating the neuroimaging-derived phenotypes with genomics deciphers various neurobiological pathways that can be leveraged for the development of novel clinical biomarkers, new treatment modalities as well as therapeutic interventions for ADHD patients. In this review, we discuss the neurobiology of ADHD with particular emphasis on structural and functional changes in the ADHD brain and their interactions with complex genomic variations utilizing imaging genetics methodologies. We also highlight the genetic variants supposedly allied with the development of ADHD and how these, in turn, may affect the brain circuit function and related behaviors. In addition to reviewing imaging genetic studies, we also examine the need for complementary approaches at various levels of biological complexity and emphasize the importance of combining and integrating results to explore biological pathways involved in ADHD disorder. These approaches include animal models, computational biology, bioinformatics analyses, and multimodal imaging genetics studies.

PET Imaging of Peripheral Benzodiazepine Receptor Standard Uptake Value Increases After Controlled Cortical Impact, a Rodent Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a chronic, life threatening injury for which few effective interventions are available. Evidence in animal models suggests un-checked immune activation may contribute to the pathophysiology. Changes in regional density of active brain microglia can be quantified in vivo with positron emission topography (PET) with the relatively selective radiotracer, peripheral benzodiazepine receptor 28 (11 C-PBR28). Phenotypic assessment (activated vs resting) can subsequently be assessed (ex vivo) using morphological techniques. To elucidate the mechanistic contribution of immune cells in due to TBI, we employed a hybrid approach involving both in vivo (11 C-PBR28 PET) and ex vivo (morphology) to elucidate the role of immune cells in a controlled cortical impact (CCI), a rodent model for TBI. Density of activated brain microglia/macrophages was quantified 120 hours after injury using the standardized uptake value (SUV) approach. Ex vivo morphological analysis from specific brain regions using IBA-1 antibodies differentiated ramified (resting) from amoeboid (activated) immune cells. Additional immunostaining of PBRs facilitated co-localization of PBRs with IBA-1 staining to further validate PET data. Injured animals displayed greater PBR28suv when compared to sham animals. Immunohistochemistry demonstrated elevated density of amoeboid microglia/macrophages in the ipsilateral dentate gyrus, corpus callosum, thalami and injury penumbra of injured animals compared to sham animals. PBR co-stained with amoeboid microglia/macrophages in the injury penumbra and not with astrocytes. These data suggest the technologies evaluated may serve as bio-signatures of neuroinflammation following severe brain injury in small animals, potentially enabling in vivo tracking of neuroinflammation following TBI and cellular-based therapies.

Traditional uses, phytochemistry and pharmacological attributes of Pterocarpus santalinus and future directions: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Pterocarpus santalinus, an ancient folk medicine, is endemic to the eastern ghats of south India, and the heartwood is prescribed since time immemorial for the mitigation of inflammatory disorders in traditional practice and ayurvedic system of medicines. AIM OF THE STUDY: This review aims to provide collective pieces of information of the traditional uses, phytochemicals, and pharmacological facets of P. santalinus, with an intuition for promoting future research to explore its pharmaceutical potential as a therapeutic agent against modern maladies. MATERIAL AND METHODS: Extensive literature search was performed to collate the data by using various electronic search engines. A network pharmacology-based approach is incorporated for validation of traditional claims orbiting around anti-inflammatory properties and directed its future exploration against obesity, ovarian inflammation, ovarian folliculogenesis, and inflammatory breast cancer. RESULTS: In a nutshell, the present review encompasses the phytochemistry, pharmacology of this species intending to sensitize the scientific community for future research on this promising plant. Nearly 85 chemical constituents are reported from the plants wherein bark and leaves are enriched with the lupane and oleanane class of triterpene while sesquiterpenes and polyphenolic compounds are predominantly present in the heartwood of the plant. Although phytochemical investigations are being reported since the mid-twentieth century however there has been recent interest in the evaluation of biological activities such as anti-inflammatory, anti-oxidant, anti-cancer, anti-viral, etc. CONCLUSION: In conclusion, a systematic phytochemical analysis and pharmacological exploration in close collaboration for establishing the therapeutic potential of the chemical constituents present in P. santalinus is recommended to substantiate the traditional claims for bringing it into the mainstream pharmaceutical and commercial utilization.