Complex interplay between RAS GTPases and RASSF effectors regulates subcellular localization of YAP.

RAS GTPases bind effectors to convert upstream cues to changes in cellular function. Effectors of classical H/K/NRAS are defined by RBD/RA domains which recognize the GTP-bound conformation of these GTPases, yet the specificity of RBD/RAs for over 160 RAS superfamily proteins remains poorly explored. We have systematically mapped interactions between BRAF and four RASSF effectors, the largest family of RA-containing proteins, with all RAS, RHO and ARF small GTPases. 39 validated complexes reveal plasticity in RASSF binding, while BRAF demonstrates tight specificity for classical H/K/NRAS. Complex between RASSF5 and diverse RAS GTPases at the plasma membrane can activate Hippo signalling and sequester YAP in the cytosol. RASSF8 undergoes liquid-liquid phase separation and resides in YAP-associated membraneless condensates, which also engage several RAS and RHO GTPases. The poorly studied RASSF3 has been identified as a first potential effector of mitochondrial MIRO proteins, and its co-expression with these GTPases impacts mitochondria and peroxisome distribution. These data reveal the complex nature of GTPase-effector interactions and show their systematic elucidation can reveal completely novel and biologically relevant cellular processes.

Mitochondrial atp1 mRNA knockdown by a custom-designed pentatricopeptide repeat protein alters ATP synthase.

Spontaneous mutations are rare in mitochondria and the lack of mitochondrial transformation methods has hindered genetic analyses. We show that a custom-designed RNA-binding pentatricopeptide repeat (PPR) protein binds and specifically induces cleavage of ATP synthase subunit1 (atp1) mRNA in mitochondria, significantly decreasing the abundance of the Atp1 protein and the assembled F1Fo ATP synthase in Arabidopsis (Arabidopsis thaliana). The transformed plants are characterized by delayed vegetative growth and reduced fertility. Five-fold depletion of Atp1 level was accompanied by a decrease in abundance of other ATP synthase subunits and lowered ATP synthesis rate of isolated mitochondria, but no change to mitochondrial electron transport chain complexes, adenylates, or energy charge in planta. Transcripts for amino acid transport and a variety of stress response processes were differentially expressed in lines containing the PPR protein, indicating changes to achieve cellular homeostasis when ATP synthase was highly depleted. Leaves of ATP synthase-depleted lines showed higher respiratory rates and elevated steady-state levels of numerous amino acids, most notably of the serine family. The results show the value of using custom-designed PPR proteins to influence the expression of specific mitochondrial transcripts to carry out reverse genetic studies on mitochondrial gene functions and the consequences of ATP synthase depletion on cellular functions in Arabidopsis.

ViLoN-a multi-layer network approach to data integration demonstrated for patient stratification.

With more and more data being collected, modern network representations exploit the complementary nature of different data sources as well as similarities across patients. We here introduce the Variation of information fused Layers of Networks algorithm (ViLoN), a novel network-based approach for the integration of multiple molecular profiles. As a key innovation, it directly incorporates prior functional knowledge (KEGG, GO). In the constructed network of patients, patients are represented by networks of pathways, comprising genes that are linked by common functions and joint regulation in the disease. Patient stratification remains a key challenge both in the clinic and for research on disease mechanisms and treatments. We thus validated ViLoN for patient stratification on multiple data type combinations (gene expression, methylation, copy number), showing substantial improvements and consistently competitive performance for all. Notably, the incorporation of prior functional knowledge was critical for good results in the smaller cohorts (rectum adenocarcinoma: 90, esophageal carcinoma: 180), where alternative methods failed.

A gain of function mutation in AKT1 increases hexokinase 2 and diminishes oxidative stress in meningioma.

Increasing evidence suggests the oncogenic role of missense mutation (AKT1-E17K) of AKT1 gene in meningiomas. Upon investigating the connection between the pro-tumorigenic role of AKT1-E17K and cellular metabolic adaptations, elevated levels of glycolytic enzyme hexokinase 2 (HK2) was observed in meningioma patients with AKT1-E17K compared to patients harboring wild-type AKT1. In vitro experiments also suggested higher HK2 levels and its activity in AKT1-E17K cells. Treatment with the conventional drug of choice AZD5363 (a pan AKT inhibitor) enhanced cell death and diminished HK2 levels in AKT1 mutants. Given the role of AKT phosphorylation in eliciting inflammatory responses, we observed increased levels of inflammatory mediators (IL-1ß, IL6, IL8, and TLR4) in AKT1-E17K cells compared to AKT1-WT cells. Treatment with AKT or HK2 inhibitors dampened the heightened levels of inflammatory markers in AKT1-E17K cells. As AKT and HK2 regulates redox homeostasis, diminished ROS generation concomitant with increased levels of NF-E2- related factor 2 (Nrf2) and superoxide dismutase 1 (SOD1) were observed in AKT1-E17K cells. Increased sensitivity of AKT1-E17K cells to AZD5363 in the presence of HK2 inhibitor Lonidamine was reversed upon treatment with ROS inhibitor NAC. By affecting metabolism, inflammation, and redox homeostasis AKT1-E17K confers a survival advantage in meningioma cells. Our findings suggest that targeting AKT-HK2 cross-talk to induce ROS-dependent cell death could be exploited as novel therapeutic approach in meningiomas.

Neutrophil-driven and interleukin-36γ-associated ocular surface inflammation in chronic Stevens-Johnson syndrome.

PURPOSE: This study aims to elucidate the tear proteome and understand the underlying molecular mechanisms involved in the ocular complications following Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: Mass spectrometry (MS) was performed to quantify the tear fluid proteins from chronic SJS/TEN patients (n = 22 eyes) and age- and gender-matched controls (n = 22 eyes). The candidate proteins were validated using ELISA (n = 80 eyes) in tear samples and immunohistochemistry (IHC; n = 12) in eyelid margin specimens. These proteins were compared for significant differences based on age, gender, disease duration, and ocular severity. RESULTS: A total of 1692 tear fluid proteins were identified, of which 470 were significantly differentially regulated in chronic SJS/TEN. The top 10 significantly upregulated proteins were neutrophil secretions including neutrophil elastase (p < .0001), defensin (p < .0001), and matrix metalloproteinase 8 (p < .0001). The presence of neutrophils was confirmed by the upregulation of IL-8 (p < .001) in tears, a key cytokine known for recruiting neutrophils. Additionally, positive expression of myeloperoxidase was observed in the keratinized eyelid margins of SJS/TEN to validate the presence of neutrophils. Among 41 unique proteins identified by MS, IL-36γ (p < .01) was expressed in three SJS/TEN patients and was confirmed in SJS/TEN tears and eyelid margins by ELISA and IHC, respectively. IL-36γ was specifically expressed in the superficial layers of eyelid margin keratinized conjunctiva. The majority of the significantly downregulated proteins were lacrimal gland secretions such as lacritin (p < .0001) and opiorphin (p < .002). Neutrophil elastase (p < .02) was significantly elevated in patients with severe eyelid margin keratinization. CONCLUSION: Our observations indicate a clear correlation between eyelid margin keratinization and the expression of IL-36γ, potentially mediated by neutrophils recruited via IL-8. Future experimental studies are needed to test the role of therapies targeting IL-8 and/or IL-36γ in reducing eyelid margin keratinization and its associated ocular complications in SJS/TEN.

Developing a model for aqueous deficient dry eye secondary to periglandular cicatrizing conjunctivitis.

PURPOSE: The current study used various techniques to develop a rabbit animal model of lacrimal gland damage caused by scarring conjunctivitis in the periglandular area. METHODS: Left eyes of New Zealand white rabbits were injected with 0.1 ml of 1M NaOH subconjunctivally around superior and inferior lacrimal gland orifices (Group 1, n = 4), touched with 1M NaOH for 100 s to the superior and inferior fornices with conjunctival denuding (Group 2; n = 4), and electrocauterization to the ductal opening area (Group 3; n = 4). The ocular surface staining, Schirmer I, lacrimal gland, and conjunctival changes were observed at baseline,1, 4, 8, and 12 weeks. The degree of glandular inflammation, conjunctival fibrosis (Masson Trichrome), and goblet cell density (PAS) were also assessed. RESULTS: At 12 weeks, the lacrimal glands of group 1 rabbits with periglandular injection showed severe inflammation with mean four foci/10HPF and a significant mean reduction in the Schirmer values by 7.6 mm (P = 0.007). Lacrimal glands had diffuse acinar atrophy, loss of myoepithelial cells, and ductular dilatation. The overlying conjunctiva showed fibrosis, goblet cell loss, and corneal vascularization in the inferotemporal quadrant. No lacrimal gland or ocular surface changes were observed in groups 2 and 3 at 12 weeks, except for localized subconjunctival fibrosis. CONCLUSION: Periglandular injection of 0.1 ml of 1M NaOH induced extensive lacrimal gland damage with reduced secretion and scarring in the subconjunctival plane compared to direct cauterization or direct NaOH contact to the ductal orifices of the rabbit lacrimal gland.

Two sisters with RSPRY1-related spondyloepimetaphyseal dysplasia.

Biallelic variants in RSPRY1 have been found to result in spondyloepimetaphyseal dysplasia. Two siblings presenting with short stature, facial dysmorphism, progressive vertebral defects, small epiphysis, cupping and fraying of metaphyses, brachydactyly, and short metatarsals harbored a homozygous missense variant c.1652G>A;p.(Cys551Tyr) in the RSPRY1 gene. The phenotype in our patients resembles spondyloepimetaphyseal dysplasia, Faden-Alkuraya type. Thus, our study provides further evidence to support the association of RSPRY1 variants with spondyloepimetaphyseal dysplasia. We observed joint dislocation as a novel clinical feature of this condition.

Indian patients with CHST3-related chondrodysplasia with congenital joint dislocations.

CHST3-related chondrodysplasia with congenital joint dislocations (CDCJD, #MIM 143095), is a rare genetic skeletal disorder caused by biallelic loss of function variants in CHST3. CHST3 is critical for the sulfation of chondroitin sulfate. This study delineates the clinical presentation of nine individuals featuring the key symptoms of CDCJD; congenital joint (knee and elbow) dislocations, short trunk short stature progressive vertebral anomalies, and metacarpal shortening. Additional manifestations include irregular distal femoral epiphysis, supernumerary carpal ossification centers, bifid humerus, club foot, and cardiac abnormalities. Sanger sequencing was carried out to investigate molecular etiology in eight patients and exome sequencing in one. Genetic testing revealed five homozygous variants in CHST3 (four were novel and one was previously reported). All these variants are located on sulfotransferase domain of CHST3 protein and were classified as pathogenic/ likely pathogenic. We thus report on nine individuals with CHST3-related chondrodysplasia with congenital joint dislocations from India and suggest monitoring the health of cardiac valves in this condition.

Metal nanoparticles to improve the heat resilience in wheat (Triticum aestivumL.).

This study evaluated the efficacy of phytogenic silver and zinc nanoparticles in improving heat resilience in various wheat varieties. The silver and zinc nanoparticles were synthesized using plant leaf extract and characterized using various techniques. Four wheat varieties (DBW187, Black Wheat, DBW 50, and PBW 621) were subjected to field trials. The random block design was used, and nanoparticles in different concentrations were applied at various growth stages and morphologically, and yield parameters were recorded. UV-vis spectroscopy spectral analysis showed peaks for Ag nanoparticles at 420 nm wavelength and Zn nanoparticles at 240 and 350 nm wavelength, depicting the preliminary confirmation of nanoparticle synthesis. Electron microscopic analysis (TEM and SEM) provided morphological insights and confirmed synthesis of fine-sized particle mostly in a range between 10 and 60 nm. Energy dispersive x-ray analysis confirmed the elemental composition of the synthesized nanoparticles, with Ag and Zn elements detected in their respective samples. It also confirmed the oxide nature of synthesized ZnNPs. Dynamic light scattering analysis provided size distribution profiles, indicating average sizes of approximately 61.8 nm for Ag nanoparticles and 46.5 nm for Zn nanoparticles. The concentrations of Ag and Zn nanoparticles in the samples were found to be 196.3 ppm and 115.14 ppm, respectively, through atomic absorption spectroscopic analysis. Fourier transform infrared spectroscopy analysis revealed characteristic functional groups present in the nanoparticles. The results of field experiments established that Ag nanoparticles at 75 ppm concentration exhibited the most significant enhancements in plant growth. Conversely, Zn nanoparticles at a 100 ppm concentration demonstrated the most substantial improvements in the growth and yield of heat-stressed wheat varieties. The study concludes that optimized concentrations of silver and zinc nanoparticles can effectively improve heat stress resilience in wheat. These findings are promising to enhance abiotic stress resilience in crops.

Neuroinflammation and Acetylcholinesterase Inhibitory Potentials of a Spiroketal-Enol Ether Polyyne Isolated from Artemisia pallens Wall. ex DC.

Artemisia pallens Wall. ex DC (Asteraceae) is cultivated for the production of high-value essential oil from its aerial biomass. In this study, the chemical composition of the root (crop-residue) essential oil was investigated for the first time, using column-chromatography, GC-FID, GC-MS, LC-QTOF, and NMR techniques, which led to the identification of twenty constituents, with isolation of (E)-2-(2',4'-hexadiynylidene)-1,6-dioxaspiro [4.5]dec-3-ene (D6). The D6 was evaluated in vitro for neuroinflammation and acetylcholinesterase inhibitory potential. It showed inhibition of neuroinflammation in a concentration-dependent manner with significant inhibition of pro-inflammatory cytokines (TNF-α and IL-6) in LPS-stimulated BV2 microglial cells. D6 did not have any significant effect on the viability of the cells at the therapeutic concentrations. D6 also has shown acetylcholinesterase inhibitory potential (51.90±1.19 %) at the concentration of log 106  nM. The results showed that D6 has a potential role in the resolution of neuroinflammation, and its acetylcholinesterase inhibitory potential directs further investigation of its role in the management of Alzheimer's disease-related pathogenesis.

Meibography-Guided Electroepilation for Congenital Distichiasis: A Novel Surgical Technique.

PURPOSE: Congenital distichiasis is managed either by ablation, using laser, cryotherapy, or electroepilation, or by surgical excision with mucous membrane grafting. Ablative procedures are usually blind as the exact depth of distichiatic eyelashes is unknown. The described surgical technique utilizes meibography for imaging the root and depth of distichiatic eyelashes that aided in performing electroepilation. METHODS: Six patients (n = 24 eyelids; mean age 15.5 ± 12.2 years) underwent infrared meibography (Oculus Keratograph 5 M) and noninvasive tear breakup time prospectively. Eyelashes were electroepilated using a premarked needle inserted at a depth based on meibography findings in 4 patients. Surgical success was defined as no distichiatic eyelash regrowth and functional success was defined as the resolution of symptoms at a minimum of 3 months of follow-up. RESULTS: All 6 patients had all 4 eyelids involved to varying degrees, with a total of 230 distichiatic eyelashes. The median number of distichiatic eyelashes was 9 in the upper eyelids and 4.5 in the lower eyelids. Meibography revealed visible distichiatic eyelash roots in 70% of eyelashes in the upper eyelid and 87.8% in the lower eyelid, respectively. The median eyelash root depth was 2.7 mm (mean 2.9 mm, range 1.8-5.4 mm). The mean noninvasive tear breakup time was 12.2 seconds despite absent or rudimentary meibomian gland segments seen on meibography. The anatomical success was 75% (12/16 eyelids), and functional success was 87.5% (7/8 eyes) at a median follow-up of 5.5 months. CONCLUSION: Preoperative infrared meibography in eyelids with congenital distichiasis helps estimate the eyelash depth and can be used to guide eyelash ablation procedures.

New Insights Into the Anatomy of the Eyelashes With Regard to Ethnic Differences Against a Clinical Background.

BACKGROUND: To investigate the root depth, root angle, and light and scanning electron microscopical anatomy of human eyelashes relevant to eyelash ablation. METHODS: Eyelash root depth, the angle between eyelash root and skin epithelium, spatial relationship, and scanning electron microscopical features of the eyelashes were studied on 4 upper and 4 lower eyelids of Caucasian (n = 4) and Indian (n = 4) cadaver heads according to a set protocol. RESULTS: There were significant differences in the mean eyelash root depth between Indians (2.3 ± 0.38 mm) and Caucasians (1.9 ± 0.26 mm; p = 0.007), as well as between upper eyelids and lower eyelids (1.9 ± 0.2 mm vs. 1.8 ± 0.1 mm). The mean angle between the lash follicle root and the skin epithelium was 75 ± 11 degrees and similar in both ethnic groups. The eyelash bulb was located close to the tarsal plate and meibomian glands and formed an angle of less than 15 degrees with the eyelash root. Scanning electron microscopy studies revealed that the eyelash bulb was 202 ± 12 µm wide in Indians and 170.6 ± 16.8 µm wide in Caucasian eyelids ( p = 0.08). The eyelashes were placed more closely in Indian eyelids than in Caucasian eyelids ( p = 0.03). The width of the cuticle layer varied between the hair shaft and the inner eyelid segment. CONCLUSIONS: There are differences in eyelash root depth, inter-eyelash distance, and cuticle thickness between Indian and Caucasian eyelids. The oblique orientation of the eyelash root and close proximity of the eyelash bulb to the tarsal plate should be kept in mind while doing the electroepilation procedure.

Acyclic monoterpenoid-rich essential oil of Cymbopogon distans mitigates skin inflammation: a chemico-pharmacological study.

The topical application of essential oils is considered an effective treatment for skin diseases. Cymbopogon distans (Nees ex Steud.) Wats (Poaceae) is a promising aromatic grass widespread in the Himalayan temperate zone. Therefore, using in-vitro and in-vivo bioassays, we examined the chemical and pharmacological characteristics of essential oil hydro-distilled from C. distans coded as CDA-01, specifically concerning skin inflammation. Characterization using GC-FID and GC-MS provided a chemical fingerprint for CDA-01, enabling the identification of 54 compounds; amongst them, citral (34.3%), geranyl acetate (21.2%), and geraniol (16.4%) were the most abundant. To examine the anti-inflammatory potential, CDA-01 treatment on LPS-stimulated macrophage cells in addition to 12-O-tetradecanoylphorbol-13-acetate (TPA) generated cutaneous inflammatory reaction in the mouse ear was assessed through quantification of the inflammatory markers. Consequently, CDA-01 demonstrated protection against inflammation caused by LPS by lowering the pro-inflammatory cytokines (IL-6 and TNF-α) level in HaCaT cells with negligible cytotoxicity. Consistent with the in-vitro findings, CDA-01 treatment reduced pro-inflammatory mediators (TNF-, IL-6, and NO) and lipid peroxidation in an in-vivo investigation. Subcutaneous inflammation in TPA-treated mice ears was similarly decreased, as evidenced by the histological and morphological studies. As a result of our findings, it is possible that CDA-01 could be an effective treatment for skin inflammation disorders.

Lacrimal gland targeted therapies for refractory epiphora: quantitative changes in the gland activity.

PURPOSE: To investigate the effect of botulinum toxin (BTX) and partial orbital lobe dacryoadenectomy (POLD) on the main lacrimal gland functions using the direct assessment of its secretory activity. METHODS: A pilot study involving 14 subjects (mean age, 42.16 years) with proximal bicanalicular block (n = 9) or complete punctal effacement (n = 5) received either intraglandular 2.5 units of BTX (n = 7) or underwent the POLD procedure (n = 7). Dynamic assessment of tear secretion from the palpebral lobes was performed as per standard protocols. The parameters studied included Schirmer I, changes in the glandular outflow, and the neurosensory secretory lag. RESULTS: Schirmer I values showed a mean reduction of 5.25 mm (range, 2-8 mm) following BTX injection, and mean tear flow decreased from 1.46 µl/min to 1.11 µl/min (P = 0.15). The POLD group showed a significant mean reduction of 0.45 µl/min in mean tear flow at 1 month (P = 0.03) and 0.32 µl/min at 3 months of follow-up (P = 0.20). However, there was no statistically significant change of the Schirmer values in the POLD group at 3 months. CONCLUSION: Direct assessment of lacrimal gland function can be used to monitor changes following the gland therapies. Although POLD shows a significant reduction in short term, significant surgical improvisation would be needed for it to be effective in long term. A larger study is ongoing to further our understanding.

Trichiasis in cicatricial ocular surface disease: a multi-center comparison of electroepilation versus eyelash resection outcomes.

PURPOSE: To evaluate the outcomes of trichiasis (excluding entropion) management in non-trachomatous cicatricial ocular surface diseases. METHODS: This is a multicenter, retrospective study of 59 patients with trichiasis who were managed using two different techniques: electroepilation using radiofrequency (RF) cautery and eyelash resection. The assessed outcomes were residual trichiasis at 6 weeks, 6, and 12 months of follow-up and the number of procedures needed. RESULTS: 41 patients (90 eyelids) underwent electroepilation, and 18 (41 eyelids) were managed with eyelash resection. All patients belonged to either Indian or Japanese ethnicity. Most patients in both groups had Stevens-Johnson Syndrome (63.4% vs. 88.9%). The mean age (43.2 vs. 46 years), disease duration (122 vs. 192.4 months), median trichiasis grade (2 vs. 2), and involvement of upper eyelids (53/90 vs. 23/41) were similar in the two groups. At six weeks, 48.9% of eyelids that underwent electroepilation had no trichiasis, and recurrences were managed with repeat electroepilation (6 eyelids) and mucous membrane grafting (10 eyelids), and 35 eyelids opted for manual epilation, giving 67.8% success at a mean follow-up of 20 months. The eyelash resection group had 75.6% success at 6 months, and recurrences were managed using lid splitting and eyelash resection, resulting in 100% success at a mean follow-up of 79 months. More interventions were needed in the electroepilation group compared to eyelash resection. CONCLUSION: Eyelash resection of the trichiatic eyelashes achieves a better success rate than electroepilation in cicatricial ocular surface disorders. Following electroepilation, one needs multiple interventions to resolve trichiasis.

Mapping soil trace metal distribution using remote sensing and multivariate analysis.

Trace metal soil contamination poses significant risks to human health and ecosystems, necessitating thorough investigation and management strategies. Researchers have increasingly utilized advanced techniques like remote sensing (RS), geographic information systems (GIS), geostatistical analysis, and multivariate analysis to address this issue. RS tools play a crucial role in collecting spectral data aiding in the analysis of trace metal distribution in soil. Spectroscopy offers an effective understanding of environmental contamination by analyzing trace metal distribution in soil. The spatial distribution of trace metals in soil has been a key focus of these studies, with factors influencing this distribution identified as soil type, pH levels, organic matter content, land use patterns, and concentrations of trace metals. While progress has been made, further research is needed to fully recognize the potential of integrated geospatial imaging spectroscopy and multivariate statistical analysis for assessing trace metal distribution in soils. Future directions include mapping multivariate results in GIS, identifying specific anthropogenic sources, analyzing temporal trends, and exploring alternative multivariate analysis tools. In conclusion, this review highlights the significance of integrated GIS and multivariate analysis in addressing trace metal contamination in soils, advocating for continued research to enhance assessment and management strategies.

Lupeol, an androgen receptor inhibitor, enhances the chemosensitivity of prostate cancer stem cells to antiandrogen enzalutamide-based therapy.

Enzalutamide is an androgen receptor (AR) antagonist commonly used in the treatment of prostate cancer (CaP). However, due to the potential toxicity and development of resistance associated with Enzalutamide-based therapy, there is a need to explore additional compounds that can enhance its therapeutic effectiveness while minimizing toxicity. Lupeol is a pharmacologically active triterpene having anticancer effects. The objective of this study was to explore Lupeol's potential in enhancing the chemosensitivity of chemoresistant CaP cells to Enzalutamide in vitro and in a mouse model. To test our hypothesis, we performed cell viability and luciferase reporter gene assay, flow cytometry, animal studies, and histopathological analysis. Finally, we analyzed the change in selective metabolites in the prostate tissue by LCMS. Results demonstrated that a combination of Lupeol and Enzalutamide could better (i) suppress the Cancer Stem Cells (CSCs) and chemoresistant cells (PTEN-CaP8 and PC3) viability and migration, (ii) increase cell cycle arrest, (iii) inhibit the transcriptional activity of AR, c-MYC, c-FLIP, and TCF (iv) inhibit tumor growth in a mouse model (v) protect Enzalutamide-induced adverse effects in prostate glands and gut tissue (vi) decrease levels of testosterone and methionine metabolites. In conclusion, Lupeol enhances the pharmacological efficacy of Enzalutamide and reduces the adverse effects. Thus, Lupeol could be a promising adjuvant for improving Enzalutamide-based treatment outcomes and warrant further research.

Biomaterials for dry eye disease treatment: Current overview and future perspectives.

Dry eye disease (DED) is an emerging health problem affecting millions of individuals every year. The current treatments for DED include lubricating eye drops and anti-inflammatory agents. These agents have to be used frequently and contain preservatives, which can damage the ocular surface. A substantially long-acting treatment with better bioavailability on the ocular surface might reduce the frequency of drug use and its side effects. This review summarizes the current state of different biomaterials-nanosystems, hydrogels, and contact lenses used as drug delivery systems in DED. The explored drugs in biomaterial formulation are cyclosporin, ocular lubricants, and topical steroids. Most of the data is from animal models where increased drug delivery and desired therapeutic effects could be obtained; however, trials involving human participants are yet to happen. There is no published study comparing the different types of biomaterials for DED use. Long-term studies evaluating their ocular toxicity and biocompatibility would enhance their transition to human use. Overall they look promising for DED treatment, but they are still in the stage of technological advancement and clinical studies.

Pharmacological, Cytotoxic, Immunostimulant, and Auto-Immune Activity of Thalloid Liverworts: An Overview.

Bryophytes have historically been employed as verdant medicine in China, Native America and India. Phenolics, glycosides, fatty acids, other rare aromatic compounds and Terpenoids found in bryophytes may help prevent cancer and other chronic disorders. Liverworts have historically been utilized in traditional medicine and also as immu-nomodulators or immunostimulants. Diterpenoids, Lipophilic mono-, sesqui- and aromatic compounds assisting to the biological activities of liverworts. For their biological functions more than 220 aromatic compounds and 700 terpenoids and other chemicals discovered in liverworts scrutinized for their pharmacological, cytotoxic, immunostimulant and auto-immune efficacies.

To decipher the phytochemical agent and mechanism for Urginea indica mediated green synthesis of Ag nanoparticles and investigation of its antibacterial activity against Methicillin-resistant Staphylococcus aureus.

Globally, Methicillin-Resistant Staphylococcus aureus bacteraemia is one of the commonest bloodstream infections associated with clinical complications and high mortality. Thence, devising effective and targeted biogenic silver based strategies are in great demand. However, limited insights regarding the biosynthesis methodologies impedes the possible scale up and commercial potentials. We, hereby demonstrate the biosynthesis of Ag nanoparticles using the phytochemical agent extracted and purified from bulb extract of Urginea indica. The chemical structure of the phytochemical agent is investigated by various chromatographic and spectroscopic techniques and was found closely relatable to N-ethylacetamide. Ag nanoparticles synthesis by this agent was found to have a strong Surface Plasmon band at 402 nm. X-ray diffraction and transmission electron microscopy further validated the formation of Ag nanoparticles with face-centred cubic structure with a size range of 20-30 nm. The biogenic metal nanoparticles have shown potential antibacterial activity against S. aureus and MRSA (within a range of 10-50 µg/mL). The nanoparticles have also shown promising anti-biofim activity against the above mentioned strains. The nanoparticles were expected to induce ROS mediated bactericidal mechamism. Cell viability and in-vitro infection studies advocate noticeable biocompatibility and future clinical potential of the developed nanoparticles against Staphylococcus infections.