Morpho-physiological and demographic responses of three threatened Ilex species to changing climate aligned with species distribution models in future climate scenarios.

The success of a species in future climate change scenarios depends on its morphological, physiological, and demographic adaptive responses to changing climate. The existence of threatened species against climate adversaries is constrained due to their small population size, narrow genetic base, and narrow niche breadth. We examined if ecological niche model (ENM)-based distribution predictions of species align with their morpho-physiological and demographic responses to future climate change scenarios. We studied three threatened Ilex species, viz., Ilex khasiana Purkay., I. venulosa Hook. f., and I. embelioides Hook. F, with restricted distribution in Indo-Burma biodiversity hotspot. Demographic analysis of the natural populations of each species in Meghalaya, India revealed an upright pyramid suggesting a stable population under the present climate scenario. I. khasiana was confined to higher elevations only while I. venulosa and I. embelioides had wider altitudinal distribution ranges. The bio-climatic niche of I. khasiana was narrow, while the other two species had relatively broader niches. The ENM-predicted potential distribution areas under the current (2022) and future (2050) climatic scenarios (General Circulation Models (GCMs): IPSL-CM5A-LR and NIMR-HADGEM2-AO) revealed that the distribution of highly suitable areas for the most climate-sensitive I. khasiana got drastically reduced. In I. venulosa and I. embelioides, there was an increase in highly suitable areas under the future scenarios. The eco-physiological studies showed marked variation among the species, sites, and treatments (p < 0.05), indicating the differential responses of the three species to varied climate scenarios, but followed a similar trend in species performance aligning with the model predictions.

Chloroplast Genome of Lithocarpus dealbatus (Hook.f. & Thomson ex Miq.) Rehder Establishes Monophyletic Origin of the Species and Reveals Mutational Hotspots with Taxon Delimitation Potential

There is phylogenetic ambiguity in the genus Lithocarpus and subfamily Quercoideae (Family: Fagaceae). Lithocarpus dealbatus, an ecologically important tree, is the dominant species among the Quercoideae in India. Although several studies have been conducted on the species' regeneration and ecological and economic significance, limited information is available on its phylo-genomics. To resolve the phylogeny in Quercoideae, we sequenced and assembled the 161,476 bp chloroplast genome of L. dealbatus, which has a large single-copy section of 90,732 bp and a small single-copy region of 18,987 bp, separated by a pair of inverted repeat regions of 25,879 bp. The chloroplast genome contained 133 genes, of which 86 were protein-coding genes, 39 were transfer RNAs, and eight were ribosomal RNAs. Analysis of repeat elements and RNA editing sites revealed interspecific similarities within the Lithocarpus genus. DNA diversity analysis identified five highly diverged coding and noncoding hotspot regions in the four genera, which can be used as polymorphic markers for species/taxon delimitation across the four genera of Quercoideae viz., Lithocarpus, Quercus, Castanea, and Castanopsis. The chloroplast-based phylogenetic analysis among the Quercoideae established a monophyletic origin of Lithocarpus, and a closer evolutionary lineage with a few Quercus species. Besides providing insights into the chloroplast genome architecture of L. dealbatus, the study identified five mutational hotspots having high taxon-delimitation potential across four genera of Quercoideae.

Formulation Development, In Vitro and In Vivo Evaluation of Topical Hydrogel Formulation of Econazole Nitrate-Loaded ß-Cyclodextrin Nanosponges.

Econazole nitrate, an antifungal drug used in the handling of skin ailments, is commercially not efficient as these ailments typically require a more elevated concentration of the drug to offer an effective pharmacological retort. Like so, it is proposed to assess the effectiveness of the topical hydrogel of econazole-loaded nanosponge in the management of skin ailment(s). Econazole nitrate-laden ß-cyclodextrin nanosponges were developed by employing the melt method using ß-cyclodextrin as the organic polymer and N,N-carbonyldiimidazole as the crosslinker. The critical factors disturbing the quality of the formulation were uniquely identified by the Ishikawa diagram, and they were optimized by the statistical experiment design concept. ß-cyclodextrin loaded nanosponges were uniquely designed using the Placket-Burman approach and optimized utilizing the Box-Behnken method. The optimized nanosponges (EN-CDN) were  421.37 ± 6.19 nm in size with an entrapment efficiency of 70.13% ± 5.73%. The topical hydrogel of nanosponges (EN-TG) was prepared using carbopol 934 and pyrrolidone as permeation enhancers. In vitro skin permeation studies affirmed the improved transport crosswise the goatskin for topical hydrogel in comparison to the marketed product. EN-TG was able to control the fungal infection in the selected animal model in comparison to the marketed preparation. Stability studies reported favorably that nanogel remained stable under normal and accelerated settings.

Nanocarriers for ocular drug delivery: current status and translational opportunity.

Ocular diseases have a significant effect on vision and quality of life. Drug delivery to ocular tissues is a challenge to formulation scientists. The major barriers to delivering drugs to the anterior and posterior segments include physiological barriers (nasolacrimal drainage, blinking), anatomical barriers (static and dynamic), efflux pumps and metabolic barriers. The static barriers comprise the different layers of the cornea, sclera, and blood-aqueous barriers whereas dynamic barriers involve conjunctival blood flow, lymphatic clearance and tear drainage. The tight junctions of the blood-retinal barrier (BRB) restrict systemically administered drugs from entering the retina. Nanocarriers have been found to be effective at overcoming the issues associated with conventional ophthalmic dosage forms. Various nanocarriers, including nanodispersion systems, nanomicelles, lipidic nanocarriers, polymeric nanoparticles, liposomes, niosomes, and dendrimers, have been investigated for improved permeation and effective targeted drug delivery to various ophthalmic sites. In this review, various nanomedicines and their application for ophthalmic delivery of therapeutics are discussed. Additionally, scale-up and clinical status are also addressed to understand the current scenario for ophthalmic drug delivery.

Ecological niche modeling as a cumulative environmental impact assessment tool for biodiversity assessment and conservation planning: A case study of critically endangered plant Lagerstroemia minuticarpa in the Indian Eastern Himalaya.

Cumulative environmental impact assessment (CEIA) at river basin level for hydroelectric projects is an evolving concept and has proved to be a useful tool to assess the cumulative impact of developmental projects on the natural ecosystems. However, the generality of CEIA studies is often contested because of methodological limitations, especially in the domain of biodiversity conservation and conservation planning. Ecological niche modeling (ENM) can be a useful tool in CEIA studies for conservation planning of threatened plants in hydroelectric project (HEP) areas. We elucidate this hypothesis taking the example of Lagerstroemia minuticarpa Debberm. ex P.C. Kanjilal, a critically endangered tree species in the Indian Eastern Himalaya. Standard ecological methods were employed to document occurrence records, estimate population size, and characterize habitats. ENM was used to estimate the species potential environmental niche and distribution areas. The possible impacts of HEPs on the potential habitats were predicted by overlaying the HEPs on the potential area map as well as using the conceptual network diagram. The study revealed that the species occupies an environmental niche characterized by humid to per-humid conditions, and is distributed mostly in the Lohit and Teesta basins. Potential areas of the species with high environmental suitability coincide with 19 HEPs, which point to a potential threat to the survival of the species. Network diagram indicated that project activities might deteriorate the habitats thereby affecting the population and regeneration of the species. Our study provides a framework for developing appropriate measures for species conservation and reintroduction at basin level using ENM.

Nanotherapies for the Treatment of Age-Related Macular Degeneration (AMD) Disease: Recent Advancements and Challenges.

Age-related Macular Degeneration (AMD) is one of the common diseases affecting the posterior part of the eye, of a large population above 45 years old. Anti-Vascular Endothelial Growth Factor- A (Anti-VEGF-A) agents have been considered and approved as therapeutic agents for the treatment of AMD. Due to the large molecular weight and poor permeability through various eye membranes, VEGF-A inhibitors are given through an intravitreal injection, even though the delivery of small therapeutic molecules by topical application to the posterior part of the eye exhibits challenges in the treatment. To overcome these limitations, nanocarrier based delivery systems have been utilized to a large extent for the delivery of therapeutics. Nanocarriers system offers prodigious benefits for the delivery of therapeutics to the posterior part of the eye in both invasive and non-invasive techniques. The nano size can improve the permeation of therapeutic agent across the biological membranes. They provide protection from enzymes present at the site, targeted delivery or binding with the disease site and extend the release of therapeutic agents with prolonged retention. This leads to improved therapeutic efficacy, patient compliance, and cost effectiveness of therapy with minimum dose associated side-effects. This review has summarized various nanocarriers explored for the treatment of AMD and challenges in translation.

Advanced Hydrogels Based Drug Delivery Systems for Ophthalmic Delivery.

Hydrogels are aqueous gels composed of cross-linked networks of hydrophilic polymers. Stimuli-responsive based hydrogels have gained focus over the past 20 years for treating ophthalmic diseases. Different stimuli-responsive mechanisms are involved in forming polymer hydrogel networks, including change in temperature, pH, ions, and others including light, thrombin, pressure, antigen, and glucose-responsive. Incorporation of nanocarriers with these smart stimuli-responsive drug delivery systems that can extend the duration of action by increasing ocular bioavailability and reducing the dosing frequency. This review will focus on the hydrogel drug delivery systems highlighting the gelling mechanisms and emerging stimuli-responsive hydrogels from preformed gels, nanogels, and the role of advanced 3D printed hydrogels in vision-threatening diseases like age-related macular degeneration and retinitis pigmentosa. It also provides insight into the limitations of hydrogels along with the safety and biocompatibility of the hydrogel drug delivery systems.

Pattern recognition by pentraxins.

Pentraxins are a family of evolutionarily conserved pattern-recognition proteins that are made up of five identical subunits. Based on the primary structure of the subunit, the pentraxins are divided into two groups: short pentraxins and long pentraxins. C-reactive protein (CRP) and serum amyloid P-component (SAP) are the two short pentraxins. The prototype protein of the long pentraxin group is pentraxin 3 (PTX3). CRP and SAP are produced primarily in the liver while PTX3 is produced in a variety of tissues during inflammation. The main functions of short pentraxins are to recognize a variety of pathogenic agents and then to either eliminate them or neutralize their harmful effects by utilizing the complement pathways and macrophages in the host. CRP binds to modified low-density lipoproteins, bacterial polysaccharides, apoptotic cells, and nuclear materials. By virtue of these recognition functions, CRP participates in the resolution of cardiovascular, infectious, and autoimmune diseases. SAP recognizes carbohydrates, nuclear substances, and amyloid fibrils and thus participates in the resolution of infectious diseases, autoimmunity, and amyloidosis. PTX3 interacts with several ligands, including growth factors, extracellular matrix component and selected pathogens, playing a role in complement activation and facilitating pathogen recognition by phagocytes. In addition, data in gene-targeted mice show that PTX3 is essential in female fertility, participating in the assembly of the cumulus oophorus extracellular matrix. PTX3 is therefore a nonredundant component of the humoral arm of innate immunity as well as a tuner of inflammation. Thus, in conjunction with the other components of innate immunity, the pentraxins use their pattern-recognition property for the benefit of the host.

A novel RBP-J kappa-dependent switch from C/EBP beta to C/EBP zeta at the C/EBP binding site on the C-reactive protein promoter.

Regulation of basal and cytokine (IL-6 and IL-1beta)-induced expression of C-reactive protein (CRP) in human hepatoma Hep3B cells occurs during transcription. A critical transcriptional regulatory element on the CRP promoter is a C/EBP binding site overlapping a NF-kappaB p50 binding site. In response to IL-6, C/EBPbeta and p50 occupy the C/EBP-p50 site on the CRP promoter. The aim of this study was to identify the transcription factors occupying the C/EBP-p50 site in the absence of C/EBPbeta. Accordingly, we treated Hep3B nuclear extract with a C/EBP-binding consensus oligonucleotide to generate an extract lacking active C/EBPbeta. Such treated nuclei contain only C/EBPzeta (also known as CHOP10 and GADD153) because the C/EBP-binding consensus oligonucleotide binds to all C/EBP family proteins except C/EBPzeta. EMSA using this extract revealed formation of a C/EBPzeta-containing complex at the C/EBP-p50 site on the CRP promoter. This complex also contained RBP-Jkappa, a transcription factor known to interact with kappaB sites. RBP-Jkappa was required for the formation of C/EBPzeta-containing complex. The RBP-Jkappa-dependent C/EBPzeta-containing complexes were formed at the C/EBP-p50 site on the CRP promoter in the nuclei of primary human hepatocytes also. In luciferase transactivation assays, overexpressed C/EBPzeta abolished both C/EBPbeta-induced and (IL-6 + IL-1beta)-induced CRP promoter-driven luciferase expression. These results indicate that under basal conditions, C/EBPzeta occupies the C/EBP site, an action that requires RBP-Jkappa. Under induced conditions, C/EBPzeta is replaced by C/EBPbeta and p50. We conclude that the switch between C/EBPbeta and C/EBPzeta participates in regulating CRP transcription. This process uses a novel phenomenon, that is, the incorporation of RBP-Jkappa into C/EBPzeta complexes solely to support the binding of C/EBPzeta to the C/EBP site.

Epidemiology and etiopathogenesis of urinary calculi in western Nepal (Pokhara).

Urinary stone disease is recorded in the literature from the dawn of the history and has spared no segment of society irrespective of age, gender, occupation and socio-economic status. It is still termed as "Refractory Disease" as complete medical management to prevent occurrence or recurrence is not so far available. We conducted a preliminary survey from the Manipal Teaching Hospital and carried out urinalyses to ascertain risk factors in the local population. This preliminary survey indicates the prevalence of stone disease is in moderate zone. Hyperoxaluria is an important risk factor in more than one fourth of the stone formers; and hypernatriuria is distinctly most common potentiating risk factor.

Spectrum of stones composition: a chemical analysis of renal stones of patients visiting NMCTH.

A general observation of clinicians suggests that the prevalence ofurolithiasis is fairly high in Kathmandu but so far no systematic study has been undertaken here to explore the etiopathogenesis of disease in this region. In this preliminary communication, we present herewith the qualitative composition of 47 renal stones collected from surgical patients admitted to NMCTH over a period of 13 months (July 2005 to July 2006). All stones were of mixed type. Calcium was present in all stones. Oxalate, phosphate and uric acid were present in 95.7%, 87.2% and 34.0% patients respectively. The probable composition, as construed from analysis, suggests that calcium oxalate stones are predominant. Strikingly, the prevalence was very high in e"20 yrs age group.

Oxidative stress and antioxidant status in cancer patients and healthy subjects, a case-control study.

Since raised oxidative stress (OS) or weak antioxidant defence or both are considered to be important players in multimechanistic pathogenesis of cancer, the present study was undertaken to evaluate their possible involvement in the pathogenesis of this disease in the local population. Levels of plasma vitamin C, vitamin E, total antioxidant activity (TAA) and thiobarbituric acid reacting substances (TBARS) as a marker of OS were measured in 20 cancer patients (Mean age 63.1 + 9.3 yr.) and 20 age, sex and socioeconomically matched healthy subjects (Mean age 63.7+7.8 yr.). Significantly low level of vitamin C (p <0.001), vitamin E (p <0.001) and TAA (p <0.003) were observed in cancer patients, whereas OS was significantly increased in patients as compared to control (p <0.003). Smokers had significantly lowered TAA and significantly raised OS than non-smokers, in both case and control groups. Tobacco chewer patients had raised OS as compared to control. This study supports the thesis that OS is a risk factor in carcinogenesis and that smoking, an established risk factor in cancer, at least partly appears through it.