Exploring the Promising Role of Guggulipid in Rheumatoid Arthritis Management: An In-depth Analysis.

BACKGROUND: Guggulipid, an oleo-gum resin extracted from the bark of Commiphora wightii of the Burseraceae family, holds a significant place in Ayurvedic medicine due to its historical use in treating various disorders, including inflammation, gout, rheumatism, obesity, and lipid metabolism imbalances. OBJECTIVE: This comprehensive review aims to elucidate the molecular targets of guggulipids and explore their cellular responses. Furthermore, it summarizes the findings from in-vitro, in-vivo, and clinical investigations related to arthritis and various inflammatory conditions. METHODS: A comprehensive survey encompassing in-vitro, in-vivo, and clinical studies has been conducted to explore the therapeutic capacity of guggulipid in the management of rheumatoid arthritis. Various molecular pathways, such as cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), PI3-kinase/AKT, JAK/STAT, nitric oxide synthase (iNOS), and NFκB signaling pathways, have been targeted to assess the antiarthritic and anti-inflammatory effects of this compound. RESULTS: The research findings reveal that guggulipid demonstrates notable antiarthritic and anti-inflammatory effects by targeting key molecular pathways involved in inflammatory responses. These pathways include COX-2, VEGF, PI3-kinase/AKT, JAK/STAT, iNOS, and NFκB signaling pathways. in-vitro, in-vivo, and clinical studies collectively support the therapeutic potential of guggulipid in managing rheumatoid arthritis and related inflammatory conditions. CONCLUSION: This review provides a deeper understanding of the therapeutic mechanisms and potential of guggulipid in the management of rheumatoid arthritis. The collective evidence strongly supports the promising role of guggulipid as a therapeutic agent, encouraging further research and development in guggulipid-based treatments for these conditions.

Isolation of bacteriophages infecting Xanthomonas oryzae pv. oryzae and genomic characterization of novel phage vB_XooS_NR08 for biocontrol of bacterial leaf blight of rice.

Bacterial leaf blight (BLB) disease of rice caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most destructive diseases worldwide in rice-growing regions. The Ineffectiveness of chemicals in disease management has increased the interest in phage therapy. In this study, we isolated 19 bacteriophages, infecting Xoo, from a rice field, which belonged to phage families Siphoviridae, Myoviridae, and Podoviridae on the basis of electron microscopy. Among 19 phages, Phage vB_XooS_NR08, a member of the Siphoviridae family, expressed antibacterial activity against all Xoo strains tested and did not lyse X. campestris and other unrelated bacterial hosts. Phage NR08 showed more than 80% viability at a temperature range of 4°C-40°C, pH range of 5-9, and direct exposure to sunlight for 2 h, whereas UV light and chemical agents were highly detrimental. In a one-step growth curve, NR08 has a 40-min latent period, followed by a 30-min burst period with a burst size of 250 particle/bacterium. The genome of NR08 is double-stranded DNA, linear having a size of 98,812 bp with a G + C content of 52.9%. Annotation of the whole-genome sequence indicated that NR08 encodes 142 putative open reading frames (ORFs), including one ORF for tRNA, namely, trna1-GlnTTG. Comparative genome analysis of NR08 showed that it shares maximum similarity with Pseudomonas phage PaMx42 (40% query coverage, 95.39% identity, and acc. Length 43,225) and Xanthomonas phage Samson (40% query coverage, 96.68% identity, and acc. Length 43,314). The average alignment percentage (AP) of NR08 with other Xoophages was only 0.32 to 1.25 since the genome of NR08 (98.8 kb) is almost double of most of the previously reported Xoophages (43-47 kb), thus indicating NR08 a novel Xoophage. In in vitro bacterial challenge assay, NR08 showed bacteriostasis up to 24 h and a 99.95% reduction in bacterial growth in 48 h. In rice pot efficacy trials, single-dose treatment of NR08 showed a significant reduction in disease up to 90.23% and 79.27% on 7 and 21 dpi, respectively. However, treatment using 2% skim milk-supplemented phage preparation was significantly less effective as compared to the neat phage preparation. In summary, this study characterized a novel Xoophage having the potential as a biocontrol agent in the mitigation of BLB in rice.

Glacial lake outburst flood risk assessment using remote sensing and hydrodynamic modeling: a case study of Satluj basin, Western Himalayas, India.

Glacier-associated hazards are becoming a common and serious challenge to the high mountainous regions of the world. Glacial lake outburst floods (GLOFs) are one of the most serious unanticipated glacier hazards, with the potential to release a huge amount of water and debris in a short span of time, resulting in the loss of lives, property, and severe damage to downstream valleys. The present study used multi-temporal Landsat and Google earth imageries to analyze the spatio-temporal dynamism of the selected glacial lake (moraine-dammed) in the Satluj basin of Western Himalayas. Furthermore, GLOF susceptibility of the lake was assessed using a multi-criteria decision-based method. The results show that the lake area has increased from 0.11 to 0.26 km2 over the past 28 years from 1990 to 2018. The susceptibility index value for the lake was calculated as 0.75, which indicates that the lake is highly susceptible to the GLOF. The depth and volume of the lake were estimated to be 16 m and 57 × 105 m3, respectively, using an empirical formula. HEC-RAS, HECGeo-RAS, and Arc-GIS software were utilized in this study to perform unsteady flow analysis and to determine the GLOF impact on the downstream area. The worst-case GLOF scenario (breach width of 75 m) was revealed during an overtopping failure of the moraine dam, resulted in a peak discharge of 4060 m3/s and releasing a total water volume of 57 × 105 m3. The breach hydrograph has been routed to calculate the spatial and temporal distribution of peak flood, inundation depth, velocity, water surface elevation, and flood peak arrival time along the river channel. The analysis further reveals that the routed flood waves reach the nearest settlement, i.e., Rajpur town, situated at a distance of 102 km in the downstream valley of the lake at 6 h after the beginning of the lake breach event with a peak discharge/flood of 1757 m3/s and maximum flow velocity of 1.5 m/s. With the ongoing climate warming and glacier retreat, moraine-dammed lakes are becoming more hazardous and thus increasing the total threat. Therefore, it is mandatory to monitor and assess such lakes at regular intervals of time to lessen the disastrous impacts of GLOFs on the livelihood and infrastructure in the downstream valleys. The findings of this study will aid in the creation of risk management plans, preparatory tactics, and risk reduction techniques for GLOF hazards in the region.

A novel approach to detect barium in gunshot residue using a handheld device: a forensic application.

The present manuscript describes an innovative handheld device for the rapid detection of barium (Ba2+) in Gunshot Residue (GSR) based on the use of gold nanomaterials capped with sodium malonate. The method depends on a shift in the Light Scattering Plasmon Resonance (LSPR) peak of malonate capped gold nanoparticles (AuNPs) from 526 nm to 610.5 nm, due to the carboxylate ion aggregation between the metal and the nanoparticles leading to a change in the color. Qualitative detection was realized by the change in the color, while for quantitative analysis a handheld device has been fabricated in-house. The results were then correlated with those of standard known methods such as UV-Vis Spectroscopy and Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES). The results showed better correlation between the fabricated device and standard methods with R2 = 0.98. It shows a linearity range from 0.01 mg mL-1 to 5 mg mL-1 with a Limit of Detection (LOD) of 0.2 mg mL-1. Furthermore, GSR samples were collected from cloth piece set at different range of shooting (i.e. 1 ft to 16.40 ft) using different ammunition to detect the presence of Ba2+ with the help of the developed device and results were found similar to those of the known methods. The hand-held device was found to be unaffected by other interfering agents (i.e. Pb2+, Sb3+, Ca2+, Cu2+, Hg2+, Mg2+, As3+, Cr3+, etc.). The results demonstrated here shows high selectivity, sensitivity and rapid method for Ba2+ detection in GSR, showing its greater potentiality in future.

Mucoadhesive gastroretentive microparticulate system for programmed delivery of famotidine and clarithromycin.

AIM: The present research was aimed to develop thiolated polyacrylic acid (TPA) based microspheres (MSPs) containing famotidine (FX) and clarithromycin (CLX). METHODS: TPA was synthesised from polyacrylic acid and l-cysteine in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC). The prepared TPA was characterised using FT-IR (Fourier transform-infra red), 1H-NMR (proton nuclear magnetic resonance) spectroscopy, P-XRD (powder X ray diffraction) method, and zeta potential. The analytical tools have supported the formation of TPA. The thiolated microspheres were prepared by emulsion solvent evaporation method using 0.75% w/v polymer concentration and stirring at 400 rpm for 8 hr. RESULTS: The average particle size and zeta potential of optimised formulation was found to be 25.2 ± 1.87 µm and -26.68 mV, respectively. The entrapment efficiency of the optimised formulation was obtained 67.20% for FX and 70.20% for CLX. The developed microspheres were swelled only in 4 h from 0.5 to 0.9. The in vitro mucoadhesive study and in vitro drug release studies demonstrated that microspheres showed mucoadhesive property. In in vitro drug release studies, the release of FX and CLX were observed to be 58.68% and 60.48%, respectively from microspheres in 8 h. The thiolated microspheres showed higher adhesion time (7.0 ± 0.8 h) in comparison to the plain microspheres (2.6 ± 0.4 h). CONCLUSION: The prepared TPA based mucoadhesive microspheres can be utilised as carriers for the treatment of peptic ulcer caused by Helicobacter pylori which will offer enhanced residence time for the rational drug combination in the gastric region.

Combination Cancer Therapy Using Multifunctional Liposomes.

Chemotherapy of cancer is still considered a complex phenomenon given that single chemotherapeutic agents cannot be administered for a long period of time because of the development of drug resistance and severe side effects. Nanodrug delivery systems (NDDSs) such as nanoparticles and liposomes are being investigated to enhance the safety and efficacy of anticancer agents. NDDS-based delivery of a single agent is not found to be effective in long-term anticancer therapy. Codelivery of more than one anticancer agent using liposomes shows great potential since it exhibits simultaneous synergistic therapeutic manifestations at the tumor site and enhances therapeutic efficacy in terms of the low-dose requirement of each agent and diminished side effects. Liposomes are lipid vesicles arranged in concentric bilayers with an aqueous core; they are versatile nanocarriers that accommodate the diverse nature of anticancer drugs (both hydrophobic and hydrophilic) at the same time. They offer a number of advantages for combinatorial drug delivery in terms of increased blood circulation, selective accumulation at tumor tissues, and stimuli responsiveness. Various combination of drugs such as paclitaxel (PTX) and topotecan, sunitinib and irinotecan, and combretastin A-4 and doxorubicin have been reported for cancer chemotherapy using liposomes. This review focuses on recent scenarios of combinatorial drug delivery using liposomes for better chemotherapeutic outcomes. This assemblage can be of great importance to researchers looking for advances in novel drug delivery approaches for better cancer treatment.

Anticancer Agents Based on Vulnerable Components in a Signalling Pathway.

Traditional cancer treatment includes surgery, chemotherapy, radiotherapy and immunotherapy that are clinically beneficial, but are associated with drawbacks such as drug resistance and side effects. In quest for better treatment, many new molecular targets have been introduced in the last few decades. Finding new molecular mechanisms encourages researchers to discover new anticancer agents. Exploring the mechanism of action also facilitates anticipation of potential resistance mechanisms and optimization of rational combination therapies. The write up describes the leading molecular mechanisms for cancer therapy, including mTOR, tyrosine Wee1 kinase (WEE1), Janus kinases, PI3K/mTOR signaling pathway, serine/threonine protein kinase AKT, checkpoint kinase 1 (Chk1), maternal embryonic leucine-zipper kinase (MELK), DNA methyltransferase I (DNMT1), poly (ADP-ribose) polymerase (PARP)-1/-2, sphingosine kinase-2 (SK2), pan-FGFR, inhibitor of apoptosis (IAP), murine double minute 2 (MDM2), Bcl-2 family protein and reactive oxygen species 1 (ROS1). Additionally, the manuscript reviews the anticancer drugs currently under clinical trials.

Inter-comparisons and applicability of CMIP5 GCMs, RCMs and statistically downscaled NEX-GDDP based precipitation in India.

The applicability of GCMs (produced at 2° to 4°) and RCMs (produced at ~0.5°) vary and they might produce lots of ambiguity in their outcomes, because of their resolutions. This is true fact and already been reported in several studies. In this study, we have explored the precipitation variabilities in India involved in different resolution climate model based data-sets such as GCMs and RCMs under two extreme Representation Concentration Pathway (RCP) experiments (e.g. RCP4.5 and RCP8.5). Precipitation inter-comparisons have been done between different resolution datasets (e.g. GCMs, RCMs, NEX-GDDP and observed precipitation) to explore precipitation ambiguity (or variabilities) and their applicability in a long-term period (1951-2100) across the India. The observed gridded precipitation (1951-2005) and NEX-GDDP datasets (2006-2100) have been used as a reference data-sets to assess the accuracy of GCMs and RCMs. Variations in precipitation trends have been explored at each grid scale utilizing non-parametric Mann-Kendall test and statistical p-value test at 95% confidence interval. Inter-comparison analysis results showed that a significant diversity existed in the precipitation amounts among all climate model datasets, which have been non-uniformly distributed across the India. Results from model inter-comparisons, percentage of change analysis and Q-Q analysis performed between GCMs versus observed precipitation, RCM versus observed precipitation, GCMs versus RCMs and RCMs versus NEX-GDDP models showed a high variability existed in precipitation amount across the India during1951-2100. In opposite, at several locations a good association in precipitation between different resolution datasets was observed. GCMs based precipitation was underestimated and RCMs showed overestimation across the India. Overall, RCMs based rainfalls have found comparatively closer to observed and NEX-GDDP based rainfalls, yet RCMs have highly overestimated in several regions of India. Seasonal trends uncertainty estimation showed a better correlation in precipitation between NEX-GDDP and RCMs, especially during monsoon and pre-monsoon season.

Poly (amidoamine) dendrimer-mediated hybrid formulation for combination therapy of ramipril and hydrochlorothiazide.

We present a dendrimer-based hybrid formulation strategy to explore the potential of poly (amidoamine) PAMAM dendrimers to be used as drug carriers for combination therapy of an anti-hypertensive drug ramipril (RAPL) and a diuretic hydrochlorothiazide (HCTZ). The drug-dendrimer complexes were prepared by phase-equilibration method. The results showed that the solubility of RAPL and HCTZ was dependent on dendrimer concentration and pH of dendrimer solution. The solubility profile of both RAPL and HCTZ dendrimer complexes illustrated a non-linear relationship with dendrimer concentration. At 0.8% (w/v) dendrimer concentration, solubility of RAPL was increased 4.91 folds with amine-terminated while for HCTZ, solubility enhancement was highest (3.72 folds) with carboxy-terminated. The complexes were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance analysis and high performance liquid chromatography. In-vitro drug dissolution performance of pure drugs, individual drug loaded dendrimer formulations and hybrid formulations was studied in USP dissolution medium (pH7.0) and in simulated gastric fluid (pH1.2). Dendrimer mediated formulations showed faster and complete dissolution compared to pure RAPL or HCTZ. Surprisingly, similar pattern of dissolution profile was established with hybrid formulations as compared to individual drug loaded dendrimers. The dendrimer-based hybrid formulations were found to be stable at dark and refrigerated conditions up to 5weeks. Conclusively, the proposed formulation strategy establishes a novel multitasking platform using dendrimer for simultaneous loading and delivery of multiple drugs for pharmaceutical applications.

Topotecan Liposomes: A Visit from a Molecular to a Therapeutic Platform.

Topotecan (TPT), a potent anticancer camptothecin analog, is well described for the treatment of ovarian cancer, but has also anticancer activity against small-cell and non-small-cell lung cancer, breast cancer, and acute leukemia. Various nanocarriers, including liposomes, have been exploited for targeted delivery of TPT. However, there are a number of challenges with TPT delivery using TPT liposomes (TLs), such as low encapsulation efficiency, physiological pH labile E ring (hydrolysis), accelerated blood clearance, multidrug resistance, and cancer metastases. This review discusses these problems and the means to overcome them, including modification of TLs using zwitterionic poly(carboxybetaine), prolongation in dosing interval (long-term therapy), and modified liposomal encapsulation techniques including active loading methods. We also explore engineered TLs (surface and integral modifications) such as PEGylated TLs, ligand-anchored TLs, and stimuli-sensitive TLs. Further, potential applications, manifestations at the molecular level, patents granted, and preclinical and clinical outlook for TLs are discussed.

Microsponges: A Pioneering Tool for Biomedical Applications.

Microparticulate drug delivery systems have been explored across the globe due to their various advantages. In 1987, Won developed microsponge systems (Micsys), also known as solid-phase porous microspheres, having numerous interconnected voids, which serve as non-collapsible residence for bioactive compounds. A Micsys particle ranges from 5 to 300 µm in size and shows a wide range of entrapment efficiency with desired release rates. This topical drug delivery system bestows a controlled release of bioactive compounds into the skin with reduced systemic side effects. Currently, the application fields of this promising system include oral, ocular, pulmonary, and parenteral delivery of bioactive compounds. In the present review, we summarize the updated biomedical application potential of Micsys as an effective drug-delivery vector, including an in-depth explanation of the drug-release kinetic models and drug-release mechanisms. We also discuss different techniques used to prepare a Micsys, along with their advantages and disadvantages. Moreover, in this review, we report a plethora of Micsys details, such as drug candidates and polymers, exploited in this field, along with marketed formulations, characterization methods, clinical perspectives, and patents received. This assembly of detailed literature summaries will contribute to future advances in the development of porous carriers.

An update on Ayurvedic herb Convolvulus pluricaulis Choisy.

Convolvulus pluricaulis Choisy (C. pluricaulis) is a perennial herb that seems like morning glory. All parts of the herb are known to possess therapeutic benefits. The plant is used locally in Indian and Chinese medicine to cure various diseases. It is used in Ayurvedic formulation for chronic cough, sleeplessness, epilepsy, hallucinations, anxiety etc. Based on the comprehensive review of plant profile, pharmacognosy, phytochemistry, pharmacological and toxicological data on the C. pluricaulis, there will be more opportunities for the future research and development on the herb C. pluricaulis. Information on the C. pluricaulis was collected via electronic search (using Pub Med, SciFinder, Google Scholar and Web of Science) and library search for articles published in peer-reviewed journals. Furthermore, information also was obtained from some local books on ethnopharmacology. This paper covers the literature, primarily pharmacological, from 1985 to the end of 2012. The C. pluricaulis is an important indigenous medicine, which has a long medicinal application for liver disease, epileptic disease, microbial disease, cytotoxic and viral diseases, central nervous system (CNS) disease in Ayurvedic medicine, traditional Chinese medicine and other indigenous medical systems. The isolated metabolites and crude extract have exhibited a wide of in vitro and in vivo pharmacological effect, including CNS depression, anxiolytic, tranquillizing, antidepressant, antistress, neurodegenerative, antiamnesic, antioxidant, hypolipidemic, immunomodulatory, analgesic, antifungal, antibacterial, antidiabetic, antiulcer, anticatatonic, and cardiovascular activity. A chemical study of this plant was then initiated, which led to the isolation of carbohydrats, proteins, alkaloids, fatty acids, steroids, coumarins, flavanoids, and glycosides as active chemicals that bring about its biological effects. A series of pharmacognostical studies of this plant show that it is a herb, its stem and leaves are hairy, more over it has two types of stomata, anisocytic and paracytic. A herb, C. pluricaulis has emerged as a good source of the traditional medicine for the treatment of liver disease, epileptic disease, microbial disease, cytotoxic and viral diseases, and CNS disease. Pharmacological results have validated the use of this species in traditional medicine. All the parts of the herb are known to possess therapeutic benefits. Expansion of research materials would provide more opportunities for the discovery of new bioactive principles from C. pluricaulis.

Herbal antioxidant in clinical practice: a review.

Antioxidant-the word itself is magic. Using the antioxidant concept as a spearhead in proposed mechanisms for staving off so-called "free-radical" reactions, the rush is on to mine claims for the latest and most effective combination of free-radical scavenging compounds. We must acknowledge that such "radicals" have definitively been shown to damage all biochemical components such as DNA/RNA, carbohydrates, unsaturated lipids, proteins, and micronutrients such as carotenoids (alpha and beta carotene, lycopene), vitamins A, B6, B12, and folate. Defense strategies against such aggressive radical species include enzymes, antioxidants that occur naturally in the body (glutathione, uric acid, ubiquinol-10, and others) and radical scavenging nutrients, such as vitamins A, C, and E, and carotenoids. This paper will present a brief discussion of some well- and little-known herbs that may add to the optimization of antioxidant status and therefore offer added preventive values for overall health. It is important to state at the outset that antioxidants vary widely in their free-radical quenching effects and each may be individually attracted to specific cell sites. Further evidence of the specialized nature of the carotenoids is demonstrated by the appearance of two carotenoids in the macula region of the retina where beta-carotene is totally absent.

Liposomes a vesicular nanocarrier: potential advancements in cancer chemotherapy.

The indispensable obligation behind the successful therapy of a disease is to deliver the effective drug/bioactive concentration with sustained release manner at the diseased organs without any exposure to the healthy tissues. Novel drug-delivery systems increase the concentration and persistence of drug at the vicinity of the target site and thereby minimize the undesired side effects of the drug to the normal tissues of body. With advances in nanotechnology, several new drug delivery approaches have become available that may fulfil the requirement of safe and effective drug therapy. Among these techniques, vesicular drug-delivery systems, particularly liposomes, are under rigorous research for their applicability to deliver FDA-approved and newer drugs. Liposomes have been widely investigated as one of the most widely used nanocarriers in cancer therapy and have shown their potential in spatial and temporal release of bioactive agents for the effective treatment of various life-threatening diseases, including cancer. Various targeted and triggered-release approaches of bioactive substances using liposomes further improve the applicability of liposomes in cancer therapeutics. Thus, keeping these points in view, the present review has been focussed on application of liposomes for development of liposome technology and its novel applications for effective cancer therapy.

Glutamate-conjugated liposomes of dopamine hydrochloride for effective management of parkinsonism's.

The blood-brain barrier restricts the brain uptake of many important hydrophilic drugs and limits their efficacy in the treatment of brain diseases because of the presence of tight junctions, high metabolic capacity, low pinocytic vesicular traffic, and efficient efflux mechanisms. In the present project, amino acid-coupled liposomes bearing dopamine HCl were prepared to deliver the drug to the brain utilizing receptor-mediated transcytosis. Uncoupled liposomes were prepared by cast film method using phosphatidylcholine and cholesterol, whereas coupled liposomes were prepared using phosphatidylcholine, cholesterol, and glutamate stearylamine conjugate in the film. These liposomes were characterized for entrapment efficiency, vesicle size, shape, in vitro drug release, and in vivo studies. The in vitro drug release was analysed by using dialysis membrane. The vesicle size was found to increase upon coupling of liposomes, whereas percent entrapment efficiency was reduced from 38.89 +/- 1.94% to 34.15 +/- 1.70% after coupling of liposomes. The in vitro percent cumulative drug release studies exhibited 51.6% drug release for uncoupled liposome and 37.9% for coupled liposome at the end of 24 h. These selected formulations were subjected for in vivo performance, which was assessed by periodic measurement of drug (chlorpromazine)-induced catatonia in albino rats (Wistar strain) and fluorescence microscopy studies of the rat brain. The results were compared with plain dopamine HCl solution. Studies revealed that dopamine HCl can be effectively delivered to brain via glutamate-coupled liposomes, and results clearly indicated the superiority of the coupled liposomal formulation over the uncoupled formulation.

The white barley mutant albostrians shows enhanced resistance to the biotroph Blumeria graminis f. sp. hordei.

We performed cytological and molecular analyses of the interaction between the biotrophic barley powdery mildew fungus Blumeria graminis f. sp. hordei and white and green leaves of the barley albostrians mutant. The leaves have the same nuclear genotype but differ from each other in respect to plastid differentiation. White leaves showed enhanced penetration resistance to B. graminis f. sp. hordei, associated with higher epidermal H2O2 accumulation beneath the appressorial germ tubes and protein cross-linking in papillae. Very low basal salicylic acid content was found in white leaves, which further confirmed that H2O2 accumulation and penetration resistance in barley are independent of salicylic acid. Expression analysis of stress and defense-related genes, including such being involved in reactive oxygen species production and cell death regulation, revealed stronger constitutive or pathogen-induced transcript accumulation in white leaves. We discuss the data on the basis of the finding that white albostrians leaves exhibit a supersusceptible interaction phenotype with the hemibiotrophic fungus Bipolaris sorokiniana.