Hyposalivation in patients with psoriasis: Association with severity, inflammatory, and anti-inflammatory cytokine biomarkers of the disease.

The aim of the study is to expound the effect of psoriasis on salivary glands by evaluating the secretion of saliva and salivary cytokine biomarkers in patients with psoriasis. This study was conducted by recruiting 120 subjects that included 60 patients diagnosed clinically with active psoriasis and 60 healthy controls who were age and gender matched to psoriatic subjects. Unstimulated whole saliva was collected from all the subjects by spitting method, and levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-2 (IL-2), and IL-10 (IL-10) were determined via enzyme-linked immunosorbent assay (BT Lab, Shanghai, China). Secretion of saliva in psoriasis patients was considerably reduced than in healthy controls. The concentrations of pro-inflammatory cytokines (TNF-α, IFN-γ, and IL-2) were significantly increased, whereas level of anti-inflammatory cytokine (IL-10) was markedly decreased in the saliva of psoriasis patients with hyposalivation compared to healthy subjects. Our results demonstrated significant negative correlation of salivary flow rates with the disease severity. No significant correlations were obtained between salivary levels of tested cytokines and salivary flow rates in our study. Findings of the study reflect inflammation of salivary glands with reduced salivary flow rates in psoriasis patients. The inflammatory responses in salivary gland tissues by virtue of increased pro-inflammatory cytokines concentrations together with lower anti-inflammatory cytokine levels may have a role in affecting the saliva secretion in psoriasis patients. Secretion of unstimulated saliva in psoriasis patients decreases with the severity and duration of the disease.

Oxidative Coupling and Self-Assembly of Polyphenols for the Development of Novel Biomaterials.

In recent years, the development of biomaterials from green organic sources with nontoxicity and hyposensitivity has been explored for a wide array of biotherapeutic applications. Polyphenolic compounds have unique structural features, and self-assembly by oxidative coupling allows molecular species to rearrange into complex biomaterial that can be used for multiple applications. Self-assembled polyphenolic structures, such as hollow spheres, can be designed to respond to various chemical and physical stimuli that can release therapeutic drugs smartly. The self-assembled metallic-phenol network (MPN) has been used for modulating interfacial properties and designing biomaterials, and there are several advantages and challenges associated with such biomaterials. This review comprehensively summarizes current challenges and prospects of self-assembled polyphenolic hollow spheres and MPN coatings and self-assembly for biomedical applications.

Developing, validating, and comparing an analytical method to simultaneously detect z-drugs in urine samples using the QuEChERS approach with both liquid chromatography and gas chromatography-tandem mass spectrometry.

Detecting z-drugs, a sedative-hypnotic medication, is also misused for criminal activities. Therefore, the analysis of urine samples is crucial for clinical and forensic purposes. We conducted a study where we developed, validated, and compared an analytical method for simultaneously detecting z-drugs in urine samples. Our approach uses the QuEChERS method for sample preparation, combined with liquid chromatography (LC) and gas chromatography (GC) coupled with tandem mass spectrometry (MS/MS). We optimized the QuEChERS method to effectively extract z-drugs from urine samples while minimizing matrix effects and achieving high recovery rates. After extraction, we split the samples into two parts for analysis using LC-MS/MS and GC-MS/MS. We validated our methods, and the results showed good linearity over a broad concentration range (1-200 ng/mL) for each z-drug. The limits of detection and quantification were within clinically relevant ranges, ensuring sensitivity for detecting z-drugs in urine samples. We compared the two chromatographic techniques by analyzing a set of urine samples spiked with known concentrations of z-drugs using both LC-MS/MS and GC-MS/MS methods and then applied to the real samples. The results were statistically analyzed to assess any significant differences in accuracy and precision above 95 %, and both methods offered reliable and consistent results with the samples as well. In conclusion, our analytical method coupled with both LC-MS/MS and GC-MS/MS using the QuEChERS approach provides a comprehensive and robust solution for the simultaneous detection of z-drugs in urine samples. The choice between the two chromatographic techniques can be based on the specific z-drugs of interest and the required analytical performance. This method holds promise for applications in clinical toxicology, forensic analysis, and monitoring z-drug usage.

Polyacrylonitrile and polyethersulfone based co-axial electrospun nanofibers for fluoride removal from contaminated stream.

Coaxial electrospun polyacrylonitrile (PAN) and polyethersulfone (PES) based nanofibers were prepared and was used for filtration of fluoride from drinking water for the first time. Well defined fiber geometry was obtained at 1 ml/h of core polymer, i.e., PES flow rate, 1.4 ml/h of shell polymer, i.e., PAN flow rate, voltage of 22 kV, while the distance between the needle tip and the collector was 15-17 cm. Increase in bead like structure in fiber strands was observed with higher PAN concentration, while it decreased for lower PES concentration, thereby giving an optimum composition (6 wt% PAN and 10 wt% PES) for uniform fiber morphology. This nanofiber, abbreviated as N2 acted as an ultrafiltration membrane having permeability in the lower range, i.e., 0.5 × 10-11 m/s Pa and its fluoride removal efficacy was 46%. Fibers were also hydrophilic with considerable porous nature. Uptake of fluoride by this N2 nanofibers were evident from binding energy of 685.2 eV during XPS analysis. It is probable that nitrile and sulfone groups present in the core and shell of the nanofibers played an active in fluoride uptake, which was estimated as 110 mg/g at 298 K. Isoelectric point was in alkaline range which promoted negative fluoride ion uptake on positive nanofiber surface. Lead played higher masking effect in the uptake of fluoride in comparison to arsenic as coexisting ion. Dynamic cross flow filtration was also studied with this nanofiber in both synthetic and real life feed solution.

Pharmacological Features of 18ß-Glycyrrhetinic Acid: A Pentacyclic Triterpenoid of Therapeutic Potential.

Glycyrrhiza glabra L. (belonging to the family Leguminosae), commonly known as Licorice, is a popular medicinal plant that has been used in traditional medicine worldwide for its ethnopharmacological efficacy in treating several ailments. Natural herbal substances with strong biological activity have recently received much attention. The main metabolite of glycyrrhizic acid is 18ß-glycyrrhetinic acid (18ßGA), a pentacyclic triterpene. A major active plant component derived from licorice root, 18ßGA has sparked a lot of attention due to its pharmacological properties. The current review thoroughly examines the literature on 18ßGA, a major active plant component obtained from Glycyrrhiza glabra L. The current work provides insight into the pharmacological activities of 18ßGA and the potential mechanisms of action involved. The plant contains a variety of phytoconstituents such as 18ßGA, which has a variety of biological effects including antiasthmatic, hepatoprotective, anticancer, nephroprotective, antidiabetic, antileishmanial, antiviral, antibacterial, antipsoriasis, antiosteoporosis, antiepileptic, antiarrhythmic, and anti-inflammatory, and is also useful in the management of pulmonary arterial hypertension, antipsychotic-induced hyperprolactinemia, and cerebral ischemia. This review examines research on the pharmacological characteristics of 18ßGA throughout recent decades to demonstrate its therapeutic potential and any gaps that may exist, presenting possibilities for future drug research and development.

Stress Response in Entamoeba histolytica Is Associated with Robust Processing of tRNA to tRNA Halves.

tRNA-derived fragments have been reported in many different organisms and have diverse cellular roles, such as regulating gene expression, inhibiting protein translation, silencing transposable elements, and modulating cell proliferation. In particular, tRNA halves, a class of tRNA fragments produced by the cleavage of tRNAs in the anti-codon loop, have been widely reported to accumulate under stress and regulate translation in cells. Here, we report the presence of tRNA-derived fragments in Entamoeba, with tRNA halves being the most abundant. We further established that tRNA halves accumulate in the parasites upon different stress stimuli such as oxidative stress, heat shock, and serum starvation. We also observed differential expression of tRNA halves during developmental changes of trophozoite-to-cyst conversion, with various tRNA halves accumulating during early encystation. In contrast to other systems, the stress response does not appear to be mediated by a few specific tRNA halves, as multiple tRNAs appear to be processed during the various stresses. Furthermore, we identified some tRNA-derived fragments associated with Entamoeba Argonaute proteins, EhAgo2-2 and EhAgo2-3, which have a preference for different tRNA-derived fragment species. Finally, we show that tRNA halves are packaged inside extracellular vesicles secreted by amoebas. The ubiquitous presence of tRNA-derived fragments, their association with the Argonaute proteins, and the accumulation of tRNA halves during multiple different stresses, including encystation, suggest a nuanced level of gene expression regulation mediated by different tRNA-derived fragments in Entamoeba. IMPORTANCE In the present study, we report for the first time the presence of tRNA-derived fragments in Entamoeba. tRNA-derived fragments were identified by bioinformatics analyses of small-RNA sequencing data sets from the parasites and also confirmed experimentally. We found that tRNA halves accumulated in parasites exposed to environmental stress or during the developmental process of encystation. We also found that shorter tRNA-derived fragments are bound to Entamoeba Argonaute proteins, indicating that they may have a potential role in the Argonaute-mediated RNA-interference pathway, which mediates robust gene silencing in Entamoeba. We noticed that in response to heat shock, the protein translation levels were elevated in the parasites. This effect was reversed in the presence of an analog of leucine, which also reduced the levels of the tRNA halves in the stressed cells. Our results suggest that tRNA-derived fragments in Entamoeba have a possible role in regulating gene expression during environmental stress.

Development and Evaluation of Biotin Functionalized Fullerenes for the Delivery of Irinotecan to Colon Tumors.

BACKGROUND: Irinotecan is a promising antitumor agent approved by FDA for intravenous use in colon cancer treatment either alone or in combination. It is a topoisomerase inhibitor and by blocking the topoisomerase-I enzyme, it causes DNA damage and results in cell death. However, it lacks selectivity and specificity for tumor cells, resulting in systemic toxicity. Thus, it is essential to reduce its side effects and improve therapeutic efficacy. OBJECTIVE: The study aimed to improve the therapeutic efficacy and minimize the toxic effects of irinotecan by developing a fullerene functionalized biotin drug delivery system and adsorbing irinotecan on the surface of the functionalized fullerene-biotin complex. METHODS: Fullerene (C60) has been observed as a potential drug delivery agent and the aminefunctionalized C60-NH2 was synthesized by functionalizing ethylenediamine on the surface of C60. The PEI functionalized C60 was further synthesized by polymerization of aziridine on the surface of C60- NH2. Biotin was attached by an amide linkage to C60-PEI and the anti-colon cancer drug irinotecan (IRI) was encapsulated (C60-PEI-Biotin/IRI). The C60-PEI-Biotin/IRI was characterized and evaluated for in vivo anti-colon cancer activity in rats and the results were compared with the parent drug irinotecan. RESULTS: The results showed that C60-PEI-Biotin/IRI conjugate had a controlled release profile according to in vitro HPLC studies. Moreover in vivo anti-tumor studies suggested that the conjugate proved to be less toxic to vital organs and had high efficacy towards tumor cells. Statistical studies confirmed less tumor index and tumor burden in the case of conjugate when compared to irinotecan. CONCLUSION: It is hypothesized that the conjugate (C60-PEI-Biotin/IRI) could cross the cell membrane easily through overexpressed biotin receptors on the cell surface of colon cancer cells and showed better efficacy and less toxicity in comparison to IRI in the colon cancer rat model.

Exploration of anticancer potential of Lantadenes from weed Lantana camara: Synthesis, in silico, in vitro and in vivo studies.

Naturally occurring pentacyclic triterpenoids and their semisynthetic analogues have engrossed increasing attention for their anticancer potential and exhibiting promising role in discovery of new anticancer agents. Present study include the semi synthetic modifications of Lantadenes from the weed Lantana carama and their structures delineation by FT-IR, 1H-NMR, 13C-NMR & mass spectroscopy. All the compounds were scrutinized for in vitro cytotoxicity, ligand receptor interaction and in vivo anticancer studies. Most of the novel analogues displayed potent antiproliferative activity against A375 & A431 cancer cell lines and found superior to parent Lantadenes. In particular, 3ß-(4-Methoxybenzoyloxy)-22ß-senecioyloxy-olean-12-en-28-oic acid was found to be most suitable compound, with IC50 value of 3.027 µM aganist A375 cell line having least docking score (-69.40 kcal/mol). Promising anticancer potential of the lead was further indicated by significant reduction in tumor volume and burden in two stage carcinoma model. These findings suggests that the Lantadene derivatives may hold promising potential for the intervention of skin cancers.

Implications of nasal delivery of bromelain on its pharmacokinetics, tissue distribution and pharmacodynamic profile-A preclinical study.

Asthma is a polygenic chronic inflammatory respiratory disease devastating the quality of life and state economies. Therefore, utilization of natural products as a therapeutic approach has attained wider consideration for development of novel drugs for asthma management. Bromelain, a mixture of natural bioactive cysteine proteases abundantly found in pineapple stem, has allured attention for its pharmacological activities. However, poor stability in gastric milieu, high dose and immunogenicity associated with prolonged use hinders its oral use. Therefore, need exists to explore alternative route of bromelain administration to achieve its plausible benefits. The present study investigated the preclinical prospects of nasal administration of bromelain on systemic bioavailability, tissue distribution and it's in vivo anti-histaminic, bronchodilator and anti-asthmatic activity in animal models. Pharmacokinetic studies revealed 1.43-fold higher relative bioavailability with faster absorption of bromelain on nasal administration at one-fourth oral dose. The enhanced cellular uptake and localization of bromelain in tissues of lung was observed significantly. Furthermore, faster onset and enhanced antihistaminic, bronchodilator and anti-asthmatic activity on bromelain's nasal administration signified faster absorption and higher in vivo stability of bromelain. Nasal administration significantly achieved decrease in level of oxidative and immunological markers along with restoration of antioxidant enzymes at considerably one-fourth dose administered orally. These findings distinctly manifested that nasal administration could be a substantial and effective route for bromelain delivery with enduring competency in asthma management.

(+)-Cyanidan-3-ol inhibits epidermoid squamous cell carcinoma growth via inhibiting AKT/mTOR signaling through modulating CIP2A-PP2A axis.

BACKGROUND: Despite recent advances in the treatment of squamous cell skin cancer (SCSC), the disease persists, and treatment resistance develops. Thus, identifying new targets and developing new therapeutic approaches showing low vulnerability to drug resistance is highly needed. PURPOSE: This study aimed to reveal a novel targeted phytotherapeutic strategy for SCSC treatment alone or in combination with standard targeted anticancer molecules. STUDY DESIGN: A library of natural products was utilized to identify molecules that inhibit the growth of skin cancer cells. The anticancer potential of the selected compound was evaluated in human skin squamous carcinoma models, in vitro and in vivo. A comprehensive ingenuity pathway analysis (IPA) strategy and molecular biology technology was adopted to investigate the therapeutic mechanisms in human SCSC. METHODS: The Matrigel invasion chamber, foci formation and soft agar colony formation assays were employed to study the cells invasion and migration potential in vitro. In vivo antitumor effects were evaluated in DMBA/TPA-induced skin papilloma and A431 human skin squamous carcinoma xenograft tumor models. An integrative IPA was employed to identify mechanisms and protein targets in human SCSC.Compounds synergies were determined by the bliss model and evaluated using human SCSC cell lines and xenograft tumors. Histological staining, immunofluorescence imaging, real-time PCR, Western blots, and flow cytometric analyses were employed to analyze apoptosis and cell signaling mechanisms. RESULTS: We identified (+)-cyanidan-3-ol (CD-3) as a selective compound for inhibiting the growth of SCSC cell lines. CD-3 inhibited tumor growth and burden without apparent toxicity and prolonged the survival of tumor-bearing mice. CD-3 inhibitory effects on SCSC growth are mediated via cell cycle arrest and caspase-dependent apoptosis induction. Mechanistic studies showed that CD-3 activates PP2A via inhibiting CIP2A and produces tumor growth inhibitory effects via promoting dephosphorylation of oncogenic AKT/mTOR signaling proteins in SCSC cells and xenograft tumors in a PP2A dependent manner. Furthermore, the combination of CD-3 and mTOR inhibitors (mTORi) synergistically reduced oncogenic phenotypes. CONCLUSIONS: Our study suggests that PP2A activation is an effective strategy for SCSC treatment and the CD-3 and mTORi combination may serve as a promising treatment for SCSC.

Synthesis and Antitumor Evaluation of Glutathione Responsive Self-Immolative Disulphide Linked Camptothecin-Biotin Conjugate.

BACKGROUND: Camptothecin is a naturally occurring alkaloid obtained from the stem wood of the Chinese tree, Camptotheca acuminata. It exerts pharmacological effects due to its ability to selectively inhibit the type-I topoisomerase DNA nuclear enzyme. Several semisynthetic analogs of camptothecin have been synthesized to date possessing antitumor activity. OBJECTIVE: Camptothecin (CPT) is one of the most promising anticancer drugs but it produces various side effects because of its non-selectivity towards cancer cells. To overcome these adverse effects, we synthesized biotin conjugate of camptothecin, which was linked via a self-immolative disulfide linker (CPT-SS-Biotin). METHODS: Biotin conjugated camptothecin linked through a disulfide bond was synthesized following schemes, and the structural characterization was carried out. The stability and drug release studies were performed in the presence of glutathione (GSH) while in vitro studies were performed on 4T1 tumor cell lines. In vivo pharmacological investigation was done using an antitumor Wistar rat model. RESULTS: The stability and drug release studies were performed in the presence of glutathione (GSH), and CPT-SSBiotin was found to be physiologically stable moiety and can only be cleaved in the presence of GSH to release free CPT. The CPT-SS-Biotin showed higher toxicity in the biotin-overexpressing 4T1 tumor cell line with a lower IC50 value (8.44 µM) compared to camptothecin alone (IC50 > 30 µM). CPT-SS-Biotin also showed 10.6% higher cellular uptake by cells in comparison to free camptothecin. The CPT-SS-Biotin was delivered to cells by binding to the biotin receptors on the cell surface, followed by energy-dependent endocytosis and internalization to cause cellular toxicity. CONCLUSION: In-vivo tumor suppression studies and in vitro cell line studies along with serological parameters and histopathological studies showed that conjugate produced a high therapeutic effect and remarkably reduced toxic effects in comparison to free CPT. The results suggested that biotinylation of camptothecin via disulfide linker can be a safe and efficacious method in cancer therapeutics.

Fullerenes For Anticancer Drug Targeting: Teaching An Old Dog A New Trick.

Fullerenes are the allotropic form of carbon consisting of a cage-like structure due to which they have attained special attention from researchers since their discovery in 1985. The unique chemical and physical properties of fullerene have attracted researchers to develop a variety of its biomedical applications. The closed cage structure of fullerenes can be used for various drug delivery applications and can also act as a medium for controlled release formulations. The development of targeted anticancer drug and drug delivery systems is one of the most challenging fields, which is widely studied and researched. In this review, we aim to provide a comprehensive review on the most recent advances in fullerenes as targeted anticancer drug delivery systems along with their therapeutic applications and challenges, thus serving the pharmaceutical and biotechnology community.

In vitro and in vivo implications of rationally designed bromelain laden core-shell hybrid solid lipid nanoparticles for oral administration in thrombosis management.

Bromelain, a dietary supplement of cysteine protease family having promising results against thrombosis, is gaining attention. Yet poor mechanical stability, gastric instability, high oral dose and poor patient compliance restricted its clinical application. Therefore, acid stable bromelain loaded hybrid solid lipid nanoparticles (Br-HNPs) were fabricated and characterized for their contribution to in-vivo stability and therapeutic efficacy in thrombosis management. Comprehensive optimization of various process and formulation variables ensued the formation of nano-sized (120.56 ± 40.12 nm) Br-HNPs with entrapment efficiency of 86.32 ± 5.56%. Spherical core shell framework of Br-HNPs prolonged drug release and provided in-vivo and storage stability at room temperature. Br-HNPs significantly inhibited platelet aggregation without affecting bleeding time and dissolved thrombus at 1.91-fold higher efficacy compared to bromelain. Furthermore, Br-HNPs prevented hypercoagulation states and suppressed cytokines production significantly (P < .05) contributing to its antiplatelet activity. These findings indicated that Br-HNPs could serve as a promising alternative to commercial therapies for management of thrombotic disorders.

Bilateral Diffuse Uveal Melanocytic Proliferation in a Patient with Recurrent Frontal Lobe Meningioma.

BACKGROUND: Bilateral diffuse uveal melanocytic proliferation (B-DUMP) is a paraneoplastic disorder that may be seen in patients with a known malignancy but more commonly is seen in those without any history of cancer. It leads to multiple uveal tumors with exudative retinal detachment along with thickening of the choroid and generally carries a poor prognosis. Its etio-pathogenesis is poorly understood but is said to involve factors secreted by the systemic malignancy that lead to proliferation of melanocytes in the uvea. METHODS: We report the presentation and management of a female with history of treated frontal lobe meningioma who presented with neovascular glaucoma along with B-DUMP and was found to have recurrence of the meningioma on neuro-imaging. CONCLUSIONS: Central nervous system meningiomas can cause B-DUMP and management of the malignancy may lead to partial resolution of posterior segment manifestations of B-DUMP.

Pediatric oral vitiligo: Case report and literature review / Vitiligo oral pediátrico: reporte de caso y revisión de la literatura

ABSTRACT: Vitiligo is an acquired hypomelanotic disorder of the skin resulting from loss of functional melanoctyes and it affects approximately 0.5-1% of individuals. 25% of vitiligo in children are diagnosed before 10 years of age. The age of onset of vitiligo in children ranges between 4 to 8 years. Depigmentation in oral cavity can be easily noted and awareness about the condition can be created if they are not aware about vitiligo elsewhere in their body and can be guided for the treatment.

RESUMEN: El vitíligo es un trastorno hipomelanótico en la piel que resulta de la pérdida de melanocitos funcionales y afecta aproximadamente al 0,5-1% de los individuos. El 25% de los casos de vitiligo en niños se diagnostican antes de los 10 años. La edad de aparición del vitiligo en los niños oscila entre los 4 y los 8 años. La despigmentación en la cavidad oral se puede notar fácilmente y se puede crear conciencia sobre la afección, si no son conscientes del vitiligo en otras partes de su cuerpo, y pueden ser guiados para el tratamiento.

Peripheral levels of C-reactive protein, tumor necrosis factor-α, interleukin-6, and interleukin-1ß across the mood spectrum in bipolar disorder: A meta-analysis of mean differences and variability.

IMPORTANCE: It is unclear whether differences exist in the magnitude and variability of pro-inflammatory mediators in the different phases of bipolar disorder (BD) and among subjects with BD, as compared to healthy controls. OBJECTIVE: To run a comparative meta-analysis of C-Reactive Protein (CRP), IL-1, IL-6, TNF-α in BD vs healthy controls, measuring mean and variability effects on all subjects. Sensitivity analyses include disease activity. DATA SOURCES: Systematic review of observational studies in PubMed and PsycInfo up to February 2nd, 2020. STUDY SELECTION: Case-control studies reporting inflammatory mediators' levels in BD and controls. DATA EXTRACTION AND SYNTHESIS: Summary distribution measures of circulating CRP, IL-1ß, IL-6, TNF-α in participants with BD and control groups were extracted. Random-effects multivariate meta-analyses were conducted based on individual study/mediator effect sizes (Hedge's g). MAIN OUTCOMES AND MEASURES: Co-primary outcomes were inflammatory mediators' levels (Hedge's g) and variability (coefficient of variance ratio (CVR)) differences between participants with BD across the mood spectrum and controls. RESULTS: Out of the initial 729 papers, 72 were assessed and then excluded after full-text review, and ultimately 53 studies were included in the systematic review, while 49 were included in the meta-analysis. The mean age was 36.96 (SD: 9.29) years, and the mean female percentage was 56.31 (SD: 16.61). CRP (g = 0.70, 95% CI 0.31-1.09, k = 37, BD = 2,215 vs HC = 3,750), IL-6 (g = 0.81, 95% CI 0.46-1.16, k = 45, BD = 1,956 vs HC = 4,106), TNF-α (g = 0.49, 95% CI 0.19-0.78, k = 49, BD = 2,231 vs HC = 3,017) were elevated in subjects with BD vs HC, but not IL-1ß (g = -0.28, 95% CI -0.68-0.12, k = 4, BD = 87 vs HC = 66). When considering euthymic, depressive, and manic episodes separately, CRP and TNF-α were elevated in both depressive and manic episodes, but not in euthymia, while IL-6 remained elevated regardless of the disease state. No difference in CVR emerged for CRP, IL-1ß, and TNF-α, while a lower CVR was observed for IL-6. When considering disease phases, CVR was higher in BD than in HCs for CRP during depressive episodes, lower for IL-6 during euthymia, and higher during manic episodes for CRP, IL-6, and TNF-α. Sensitivity analyses after excluding outliers identified with funnel plot visual inspection, low-quality studies, and considering only studies matched per body mass index confirmed the main results. Meta-regression showed that age (IL-6, TNF-α), gender (CRP), duration of illness (CRP) moderated elevated individual inflammatory levels. CONCLUSIONS AND RELEVANCE: Peripheral pro-inflammatory marker elevations were confirmed in BD. CRP and TNF-α could represent state markers, as they were only elevated during mood episodes, while IL-6 appeared to be a trait marker for BD. Increased variability of specific inflammatory mediators in specific disease active states suggests that a subset of subjects with BD may exhibit elevated inflammation as part of a manic or depressive episode.

Exploration of bromelain laden nanostructured lipid carriers: An oral platform for bromelain delivery in rheumatoid arthritis management.

Bromelain, a cysteine protease exhibits promising potential in amelioration of wide variety of inflammatory disorders. Its denaturation or aggregation in gastric milieu depletes its therapeutic potential along with unpredictable prophylactic hypersensitivity reactions. Hence, efficient carrier system to improve bromelain's stability and avoid related side effects is of utmost importance. Therefore, present investigation was undertaken to prepare bromelain loaded nanostructured lipid carriers (Br-NCs) with high drug loading, stability and efficacy in rheumatoid arthritis management. Br-NCs fabricated via double emulsion solvent evaporation method were characterized for physical properties, morphology and stability. Optimized batch exhibited spherical shape, nanometric size (298.23 nm) and entrapment efficiency ~77% with sustained release behavior and improved gastric stability. Br-NCs exhibited 4.63-folds improvement in shelf-life compared to bromelain at room temperature. The protective potential of orally administered Br-NCs in rheumatoid arthritis was evaluated via assessing arthritis severity in wistar rats along with biochemical, hematological and immunological parameters. Br-NCs remarkably (p < 0.05) diminished paw edema, joint stiffness, mechanical allodynia and tissue damage along with alleviation of oxidative stress and immunological markers. Radiological joint alterations were also notably preserved with Br-NCs. Thus, preclinical studies distinctly manifested that Br-NCs formulation opens new avenue for development of novel effective therapeutic modality for rheumatoid arthritis management.

Autosomal dominant neuronal ceroid lipofuscinosis: Clinical features and molecular basis.

The neuronal ceroid lipofuscinoses (NCLs) are at least 13 distinct progressive neurodegenerative disorders unified by the accumulation of lysosomal auto-fluorescent material called lipofuscin. The only form that occurs via autosomal-dominant inheritance exhibits adult onset and is sometimes referred to as Parry type NCL. The manifestations may include behavioral symptoms followed by seizures, ataxia, dementia, and early death. Mutations in the gene DNAJC5 that codes for the presynaptic co-chaperone cysteine string protein-α (CSPα) were recently reported in sporadic adult-onset cases and in families with dominant inheritance. The mutant CSPα protein may lead to disease progression by both loss and gain of function mechanisms. Iron chelation therapy may be considered as a possible pharmaceutical intervention based on our recent mechanism-based proposal of CSPα oligomerization via ectopic Fe-S cluster-binding, summarized in this review.

Isolation optimisation, synthesis, molecular docking and in silico ADMET studies of lantadene a and its derivatives.

A simple and economical method was developed for the extraction and isolation of pentacyclic triterpenoid lantadene A from the leaves of Lantana camara. The lantadene A displays significant anti-inflammatory and anticancer properties via the inhibition of IKK-mediated NF-κB protein. Therefore, the derivatives of lantadene A were synthesised to further optimise the pharmacophore for anti-inflammatory and anticancer activities. The synthesised compounds were docked into the active site of IKK to find the most potent inhibitor of IKK. Molecular docking studies revealed that 3ß,22ß-diisobutyl substituted lantadene derivative (10) binds to the IKK protein with the highest affinity. Furthermore, in the in silico ADMET studies, the lead IKK inhibitor (10) was found to be Ames non-toxic, non-carcinogen, and a weak inhibitor of hERG.[Figure: see text].