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Since the overall glioma mass and its subcomponents-enhancing region (malignant part of the tumor), non-enhancing (less aggressive tumor cells), necrotic core (dead cells), and edema (water deposition)-are complex and irregular structures, non-Euclidean geometric measures such as fractal dimension (FD or "fractality") and lacunarity are needed to quantify their structural complexity. Fractality measures the extent of structural irregularity, while lacunarity measures the spatial distribution or gaps. The complex geometric patterns of the glioma subcomponents may be closely associated with the grade and molecular landscape. Therefore, we measured FD and lacunarity in the glioma subcomponents and developed machine learning models to discriminate between tumor grades and isocitrate dehydrogenase (IDH) gene status. 3D fractal dimension (FD3D) and lacunarity (Lac3D) were measured for the enhancing, non-enhancing plus necrotic core, and edema-subcomponents using preoperative structural-MRI obtained from the The Cancer Genome Atlas (TCGA) and University of California San Francisco Preoperative Diffuse Glioma MRI (UCSF-PDGM) glioma cohorts. The FD3D and Lac3D measures of the tumor-subcomponents were then compared across glioma grades (HGGs: high-grade gliomas vs. LGGs: low-grade gliomas) and IDH status (mutant vs. wild type). Using these measures, machine learning platforms discriminative of glioma grade and IDH status were developed. Kaplan-Meier survival analysis was used to assess the prognostic significance of FD3D and Lac3D measurements. HGG exhibited significantly higher fractality and lower lacunarity in the enhancing subcomponent, along with lower fractality in the non-enhancing subcomponent compared to LGG. This suggests that a highly irregular and complex geometry in the enhancing-subcomponent is a characteristic feature of HGGs. A comparison of FD3D and Lac3D between IDH-wild type and IDH-mutant gliomas revealed that mutant gliomas had ~2.5-fold lower FD3D in the enhancing-subcomponent and higher FD3D with lower Lac3D in the non-enhancing subcomponent, indicating a less complex and smooth enhancing subcomponent, and a more continuous non-enhancing subcomponent as features of IDH-mutant gliomas. Supervised ML models using FD3D from both the enhancing and non-enhancing subcomponents together demonstrated high-sensitivity in discriminating glioma grades (~97.9%) and IDH status (~94.4%). A combined fractal estimation of the enhancing and non-enhancing subcomponents using MR images could serve as a non-invasive, precise, and quantitative measure for discriminating glioma grade and IDH status. The combination of 2-hydroxyglutarate-magnetic resonance spectroscopy (2HG-MRS) with FD3D and Lac3D quantification may be established as a robust imaging signature for glioma subtyping., (© 2024 John Wiley & Sons Ltd.)

Withania somnifera, the plant named Indian ginseng, Ashwagandha, or winter cherry, has been used since ancient times to cure various health ailments. Withania somnifera is rich in constituents belonging to chemical classes like alkaloids, saponins, flavonoids, phenolic acids, and withanolides. Several chemotypes were identified based on their phytochemical composition and credited for their multiple bioactivities. Besides, exhibiting neuroprotective, immunomodulatory, adaptogenic, anti-stress, bone health, plant has shown promising anti-cancer properties. Several withanolides have been reported to play a crucial role in cancer; they target cancer cells by different mechanisms such as modulating the expression of tumor suppressor genes, apoptosis, telomerase expression, and regulating cell signaling pathway. Though, many treatments are available for cancer; however, to date, no assured reliable cure for cancer is made available. Additionally, synthetic drugs may lead to development of resistance in time; therefore, focus on new and natural drugs for cancer therapeutics may prove a longtime effective alternative. This current report is a comprehensive combined analysis upto 2023 with articles focused on bio-activities of plant Withania somnifera from various sources, including national and international government sources. This review focuses on understanding of various mechanisms and pathways to inhibit uncontrolled cell growth by W. somnifera bioactives, as reported in literature. This review provides a recent updated status of the W. somnifera on pharmacological properties in general and anti-cancer in particular and may provide a guiding resource for researchers associated with natural product-based cancer research and healthcare management., (© 2024 John Wiley & Sons Ltd.)

The review article serves as a mini directory of medicinal plants (662 medicinal plants have been identified) that have been investigated for antiviral property between 2015 and 2019. Data have been extracted from Scopus using specific keywords followed by manual sorting to avoid any duplication. Critical analyses of handpicked data have been presented. Mapping of medicinal plants, followed by critical analysis on the families and plant parts investigated in the said tenure, and its correlation with the participating countries and virus types have been critically analyzed. Interceptive role of phytochemicals in impeding viral replication has also been taken note of. Emphasis on India's exploration of various medicinal plants has also been given. Also presents a tutelage, which is likely to revive the interest in natural products for search of potential antivirals. This review is expected to serve as a rich data bank and as a guiding principle for researchers who are planning to explore medicinal plants in search for potential antiviral. It is time that researchers need to revisit their countries' own history of traditional medicine to predict something worthful in future., (© 2021 John Wiley & Sons Ltd.)

Tephrosia purpurea (L.) Pers. is a well-known plant in Ayurveda and named "Sarwa wranvishapaka" for its property to heal wounds. Traditionally, it is practiced for impotency, asthma, dyspepsia, hemorrhoids, syphilis gonorrhea, rheumatism, enlargement of kidney and spleen. It is an important component of herbal preparations like Tephroli and Yakrifti used to cure liver disorders. Various phytocompounds including pongamol, purpurin, purpurenone, tephrosin, bulnesol, tephrostachin, β-sitosterol, and so on have been reported. Modern pharmacological studies have shown that the plant have wound healing, antileishmanial, anticarcinogenic, antimicrobial, antioxidant, hepatoprotective, antifertility, antispermatogenic, anti-diarrheal, diuretic, and insecticidal properties. Acetylcholinesterase inhibitory action reported from this plant aids its utilization for the development of drugs for Alzheimer's and dementia neurological disorders. Among the known active compounds of T. purpurea, tephrostachin is responsible for antiplasmodial activity, tephrosin, pongaglabol, and semiglabrin exerts antiulcer activity while quercetin, rutin, β-sitosterol, and lupeol are mainly responsible for its anti-inflammatory and anti-cancer properties. From different toxicological studies, concentrations up to 2,000 mg/kg were considered safe. The present review comprehensively summarizes the ethnomedicine, phytochemistry, pharmacology, and toxicology of T. purpurea. Further research on elucidation of the structure-function relationship among active compounds, understanding of multi-target network pharmacology and clinical applications will intensify its therapeutic potential., (© 2020 John Wiley & Sons, Ltd.)

Ageratum conyzoides L. (Asteraceae) is an invasive aromatic herb with immense therapeutic importance. The herb is distributed in tropical and subtropical regions. A. conyzoides has imparted numerous ethnomedicinal uses because it has been used to cure various ailments that include leprosy, skin disorders, sleeping sickness, rheumatism, headaches, dyspnea, toothache, pneumonia and many more. A number of phytoconstituents have been scrutinized such as alkaloids, flavonoids, terpenes, chromenes, and sterols from almost every part of this plant. These phytoconstituents have shown diverse pharmacological properties including antimicrobial, anti-inflammatory, analgesic, antioxidant, anticancer, antiprotozoal, antidiabetic, spasmolytic, allelopathy, and many more. The plant A. conyzoides has provided a platform for doing pharmaceutical and toxicological research in order to isolate some promising active compounds and authenticate their safety in clinical uses. A. conyzoides provides principal information for advanced studies in the field of pharmaceutical industries and agriculture. Present review article describes the cytogenetics, ethnobotany, phytochemistry, pharmacology, and toxicological aspects of A. conyzoides., (© 2019 John Wiley & Sons, Ltd.)

Immunization with radiation-attenuated Plasmodium sporozoites (RAS) induces sterile and long-lasting protective immunity. Although intravenous (IV) route of RAS immunization is reported to induce superior immunity compared to intradermal (ID) injection, its role in the maintenance of sterile immunity is yet to be understood. We investigated whether the route of homologous sporozoite challenge of Plasmodium berghei (Pb) RAS-immunized mice would influence the longevity of protection. C57BL/6 mice immunized with Pb-RAS by IV were 100% protected upon primary IV/ID sporozoite challenge. In contrast, ID immunization resulted in 80% protection, regardless of primary challenge route. Interestingly, the route of primary challenge was found to bring difference in the maintenance of sterile protection. While IV Pb RAS-immunized mice remained protected at all challenges regardless of the route of primary challenge, ID Pb-RAS-immunized mice receiving ID primary challenge became parasitaemic upon secondary IV challenge. Significantly, primary IV challenge of Pb RAS ID-immunized mice resulted in 80% and 50% survival at secondary and tertiary challenges, respectively. According to phenotypically diverse liver CD8 + T cells, the percentages and the numbers of both CD8 + T effector memory and resident memory cells were significantly higher in IV than in ID Pb RAS-immunized mice. IFN-γ-producing CD8 + T cells specific to Pb TRAP 130 and MIP-4-Kb-17 were also found significantly higher in IV mice than in ID mice. The enhanced T-cell generation and the longevity of protection appear to be dependent on the parasite load during challenge when infection is tolerated under suboptimal CD8 + T-cell response., (© 2019 John Wiley & Sons Ltd.)

Purpose: To develop a method that can separate and quantify the fast (>1 kHz) and slow exchange transfer and magnetization transfer components in Z-spectra., Methods: Z-spectra were recorded as a function of mixing time using a train of selective pulses providing variable-delay multipulse build-up curves. Fast and slow transfer components in the Z-spectra were separated and quantified on a voxel-by-voxel basis by fitting the mixing time-dependent CEST signal using a 3-pool model., Results: Phantom studies of glutamate solution, bovine serum albumin solution, and hair conditioner showed the capability of the proposed method to separate fast and slow transfer components. In vivo mouse brain studies showed a strong contrast between white matter and gray matter in the slow-transferring map, corresponding to an asymmetric component of the conventional semisolid magnetization transfer contrast. In addition, a fast-transferring proton map was found that was homogeneous across the brain and attributed to the total contributions of the fast-exchanging protons from proteins, metabolites, and a symmetric magnetization transfer contrast component., Conclusions: This new method provides a simple way to extract fast and slow transfer components from the Z-spectrum, leading to novel MRI contrasts, and providing insight into the different magnetization transfer contrast contributions., (© 2018 International Society for Magnetic Resonance in Medicine.)

Purpose: To investigate the use of natural dextrans as nano-sized chemical exchange saturation transfer (CEST) MRI probes for characterizing size-dependent tumor vascular permeability., Methods: Dextrans of different molecular weight (10, 70, 150, and 2000 kD) were characterized for their CEST contrast. Mice (N = 5) bearing CT26 subcutaneous colon tumors were injected intravenously with 10 kD (D10, 6 nm) and 70 kD (D70, 12 nm) dextran at a dose of 375 mg/kg. The CEST-MRI signal in the tumors was assessed before and approximately 40 min after each injection using a dynamic CEST imaging scheme., Results: All dextrans of different molecular weights have a strong CEST signal with an apparent maximum of approximately 0.9 ppm. The detectability and effects of pH and saturation conditions (B 1 and T sat ) were investigated. When applied to CT26 tumors, the injection of D10 could produce a significant "dexCEST" enhancement in the majority of the tumor area, whereas the injection of D70 only resulted in an increase in the tumor periphery. Quantitative analysis revealed the differential permeability of CT26 tumors to different size particles, which was validated by fluorescence imaging and immunohistochemistry., Conclusions: As a first application, we used 10- and 70-kD dextrans to visualize the spatially variable, size-dependent permeability in the tumor, indicating that nano-sized dextrans can be used for characterizing tumor vascular permeability with dexCEST MRI and, potentially, for developing dextran-based theranostic drug delivery systems. Magn Reson Med 79:1001-1009, 2018. © 2017 International Society for Magnetic Resonance in Medicine., (© 2017 International Society for Magnetic Resonance in Medicine.)

Purpose: To develop an on-resonance variable delay multipulse (VDMP) scheme to image magnetization transfer contrast (MTC) and the chemical exchange saturation transfer (CEST) contrast of total fast-exchanging protons (TFP) with exchange rate above approximately 1 kHz., Methods: A train of high power binomial pulses was applied at the water resonance. The interpulse delay, called mixing time, was varied to observe its effect on the water signal reduction, allowing separation and quantification of MTC and CEST contributions as a result of their different proton transfer rates. The fast-exchanging protons in CEST and MTC are labeled together with the short T 2 components in MTC and separated out using a variable mixing time., Results: Phantom studies of selected metabolite solutions (glucose, glutamate, creatine, myo-inositol), bovine serum albumin (BSA), and hair conditioner show the capability of on-resonance VDMP to separate out exchangeable protons with exchange rates above 1 kHz. Quantitative MTC and TFP maps were acquired on healthy mouse brains using this method, showing strong gray/white matter contrast for the slowly transferring MTC protons, whereas the TFP map was more uniform across the brain but somewhat higher in gray matter., Conclusions: The new method provides a simple way of imaging fast-exchanging protons and MTC components with a slow transfer rate. Magn Reson Med 77:730-739, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

Purpose: To propose and evaluate a model for the blood water T1 that takes into account the effects of hematocrit fraction, oxygenation fraction, erythrocyte hemoglobin concentration, methemoglobin fraction, and plasma albumin concentration., Methods: Whole blood and lysed blood T1 data were acquired at magnetic fields of 3 Tesla (T), 7T, 9.4T, and 11.7T using inversion-recovery measurements and a home-built blood circulation system for maintaining physiological conditions. A quantitative model was derived based on multivariable fitting of this data., Results: Fitting of the model to the data allowed determination of the different parameters describing the blood water T1 such as those for the diamagnetic and paramagnetic effects of albumin and hemoglobin, and the contribution of methemoglobin. The model correctly predicts blood T1 at multiple fields, as verified by comparison with existing literature., Conclusion: The model provides physical and physiological parameters describing the effects of hematocrit fraction, oxygenation, hemoglobin concentration, methemoglobin fraction, and albumin concentration on blood water T1 . It can be used to predict blood T1 at multiple fields. Magn Reson Med 76:270-281, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

The effects of a 90-day oral administration of water and alcohol extracts of dried calyx of Hibiscus sabdariffa were evaluated in albino rats. Haematological, biochemical and histopathological changes were monitored every 30 days.The death of the animals was preceded by a severe loss in weight, accompanied with diarrhoea in animals on the 2000 mg/kg dose. There was an increase in food intake (g) per kg body weight per day in the aqueous (A) and ethanol (E) 300 mg/kg extract groups. Significant reductions in the erythrocyte count with no difference in total leucocyte count were observed. The activity of aspartate aminotransferase (AST) was enhanced by the administration of aqueous and 50% ethanol extract with a significant increase in its level at higher doses (p < 0.05). Alanine aminotransferase (ALT) and creatinine levels were significantly affected by all the extracts at the different dose levels. However, aqueous extracts exhibited a significant increase in creatinine levels (p < 0.05) at higher doses. The cholesterol levels were generally not significantly affected by the extracts. No significant histopathological changes were observed, although there was a significant reduction in the weight of the spleen of the animals administered with ethanol and water extracts when compared with the control (p < 0.01). Other organs were of the same relative weight., ((c) 2008 John Wiley & Sons, Ltd.)

Entamoeba histolytica, the protozoan parasite, is the causative agent of amoebiasis. The degree of virulence, as inferred from invasiveness, of potentially pathogenic strains may be regulated by both host and parasite factors that determine the gut environment. One such factor that plays an important role is the bacterial flora in the gut. Previous studies have clearly shown that bacterial flora is an important determinant of virulence in E. histolytica. However, the exact nature of changes induced in E. histolytica in response to bacteria and their role in virulence is not clear. In this study the levels of a number of molecules potentially important in virulence mechanisms were determined in E. histolytica cells grown with and without normal human bacterial flora, using enzyme-linked immunosorbent assay. Significant changes were observed only after the E. histolytica cells had been adapted to grow with bacterial flora for a number of generations, and not in short term culture.