Natural Immunomodulatory Agents as a Complementary Therapy for Poxviruses.

Poxviruses target innate immunity mediators such as tumor necrosis factors, interleukins, interferons, complement, and chemokines. It also targets adaptive immunity such as CD4+ T cells, CD4+ T cells, and B cells. Emerging of the recent epidemic of monkeypox virus (MPXV), a zoonotic disease native to Central and Western Africa, besides the lack of permitted treatments for poxviruses infections, encouraged researchers to identify effective inhibitors to help in preventing and treating poxviruses infections. Natural bioactive components, particularly polyphenolics, are promising for creating powerful antioxidants, anti-inflammatory, immune-stimulating, and antiviral agents. As a result, they are potentially effective therapies for preventing and treating viral diseases, such as infections caused by poxviruses including the recent pandemic MPXV. Polyphenolics: rosmarinic acid, caffeic acid, resveratrol, quercitrin, myricitrin, gingerol, gallotannin, and propolis-benzofuran A, as well as isoquinoline alkaloids: galanthamine and thalimonine represent prospective antiviral agents against MPXV, they can inhibit MPXV and other poxviruses via targeting different viral elements including DNA Topoisomerase I (TOP1), Thymidine Kinase (TK), serine/threonine protein kinase (Ser/Thr kinase), and protein A48R. The bioactive extracts of different traditional plants including Guiera senegalensis, Larrea tridentata, Sarracenia purpurea, Kalanchoe pinnata (Lam.) Pers., Zingiber officinale Roscoe, Quercus infectoria, Rhus chinensis, Prunella vulgaris L., Salvia rosmarinus, and Origanum vulgare also can inhibit the growth of different poxviruses including MPXV, vaccinia virus (VACV), variola virus, buffalopox virus, fowlpox virus, and cowpox virus. There is an urgent need for additional molecular studies to identify and confirm the anti-poxviruses properties of various natural bioactive components, especially those that showed potent antiviral activity against other viruses.

Tannic acid coated nanosuspension for oral delivery of chrysin intended for anti-schizophrenic effect in mice.

Chrysin is a flavonoid drug with numerous therapeutic activities. It suffers from low intestinal absorption owing to its hydrophobicity. Therefore, the aim of this study is to exploit the efficient technique of nanosuspension (NSP) to formulate chrysin-NSP coated with tannic acid (TA) to improve the solubility and anti-schizophrenic activity of chrysin. A 23 full factorial design was constructed where the independent factors were type of polymer, surfactant concentration (0.5 or 1 %) and the aqueous phase volume (5 or 15 mL), while the dependent responses were the particle size (PS) of the obtained formulation as well as the % chrysin dissolved after 2 h (Q2h). The optimum formulation (NSP-4) composed of 1 % PEG 400 and 1 % Cremophor RH40 in 15 mL aqueous phase. It achieved a PS and Q2h values of 108.00 nm and 38.77 %, respectively. NSP-4 was then coated with TA (TA-coated NSP-4) for further enhancement of chrysin solubility. TA-coated NSP-4 revealed PS and zeta potential values of 150 ± 14 nm and -32.54 ± 2.45 mV, respectively. After 6 h, chrysin dissolved % were 53.97 and 80.22 for uncoated NSP-4 and TA-coated NSP-4, respectively, compared with only 9.47 for free chrysin. The developed formulations and free chrysin were assessed regarding their effect on schizophrenia induced in mice by cuprizone (CPZ). Treatment with the developed formulations and free chrysin ameliorated demyelination and behavioral deficit induced by CPZ via elevating MBP and PI3K/PKC activities as well as reducing GFAP expression levels. The developed formulations and free chrysin inhibited Galactin-3 and TGF-ß expressions and stimulated GST antioxidant enzyme. Furthermore, they maintained the balances in glutamatergic and dopaminergic neurotransmission via modulation on neuregulin-1 and alleviated nuclear pyknosis and degeneration in the neurons. The order of activity was: TA-coated NSP-4 > NSP-4 > free chrysin.

Phoenix dactylifera L.: An Overview of Phytochemical Constituents and Impact on Women's Health.

Genus Phoenix is one of the most common genera in the palm family (Arecaceae) with 17 species distributed around the world. Phoenix spp. have been used for centuries as food and medicine by different cultures. Phoenix dactylifera L. (date palm) is the utmost significant, particularly in the Middle East and Arab World. This review displays the main phytochemical constituents of P. dactylifera and describes its impact on women's health from menarche to menopause, effects on fertility and during certain health conditions. Studies revealed that P. dactylifera is a valuable source of both primary and secondary metabolites including sugars, amino acids, phenolic acids, flavonoids, proanthocyanidins, carotenoids, phytosterols, terpenes and sphingolipids, besides vitamins and minerals which is reflected on its wide array of pharmacologic activities viz. immunomodulatory, antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, anti-mutagenic and anti-cancer activities. For millennia,  P. dactylifera has been utilized for food and medicine, being justified by  profuse studies. However, further research is still required to deeply understand their clinical implications, especially concerning women's health. Moreover, there are other Phoenix species that still need to be investigated to learn more about their undiscovered phytochemical components and biological activities.

Fast skin healing chitosan/PEO hydrogels: In vitro and in vivo studies.

Due to its outstanding qualities, particularly when it takes the shape of hydrogels, chitosan is a well-known biological macromolecule with many applications. When chitosan hydrogels are modified with other polymers, the desirable function as skin regeneration hydrogels is compromised; nevertheless, the mechanical properties can be improved, which is crucial for commercialization. In this study, for the first time, bimetallic zinc silver metal-organic frameworks (ZAg MOF) loaded with ascorbic acid were added to chitosan/polyethylene oxide (PEO) based interpenetrating polymer network (IPN) hydrogels that were crosslinked with biotin to improve their antimicrobial activity, mechanical characteristics, and sustainable treatment of wounds. Significant changes in the microstructure, hydrophilicity level, and mechanical properties were noticed. Ascorbic acid release patterns were upregulated in an acidic environment pH (5.5) that mimics the initial wound pH. Impressive cell viability (98 %), antimicrobial properties, and almost full skin healing in a short time were achieved for the non-replaceable chitosan/PEO developed hydrogels. Enhancing the wound healing of the treated animals using the prepared CS/PEO hydrogel dressing was found to be a result of the inhibition of dermal inflammation via decreasing IL-1ß, suppressing ECM degradation (MMP9), stimulating proliferation through upregulation of TGF-ß and increasing ECM synthesis as it elevates collagen 1 and α-SMA contents. The findings support the implementation of developed hydrogels as antimicrobial hydrogels dressing for fast skin regeneration.

Molecular networking-guided investigation of the secondary metabolome of four Morus species and their in vivo neuroprotective potential for the mitigation of Alzheimer's disease.

Alzheimer's Disease (AD) is a fatal age-related neurodegenerative condition with a multifactorial etiology contributing to 70% of dementia globally. The search for a multi-target agent to hit different targets involved in the pathogenesis of AD is crucial. In the present study, the neuroprotective effects of four Morus extracts were assessed in LPS-induced AD in mice. Among the studied species, M. macroura exhibited a profound effect on alleviating the loss of cognitive function, improved the learning ability, restored the acetylcholine esterase (AChE) levels to normal, and significantly reduced the tumor necrosis factor alpha (TNF-α) brain content in LPS-treated mice. To investigate the secondary metabolome of the studied Morus species, ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-HRMS/MS), aided with feature-based molecular networking, was employed. Among the annotated features, aryl benzofurans and prenylated flavonoids were suggested as being responsible for the observed neuroprotective effect. Furthermore, some of the detected metabolites were proposed as new natural products such as moranoline di-O-hexoside (1), isomers of trimethoxy-dihydrochalcone-O-dihexoside (59 & 76), (hydroxy-dimethoxyphenyl)butenone-O-hexoside (82), and O-methylpreglabridin-O-sulphate (105). In conclusion, our findings advocate the potential usage of M. macroura leaves for the management of AD, yet after considering further clinical trials.

Phytochemical Elucidation and Effect of Maesa indica (Roxb.) Sweet on Alleviation of Potassium Dichromate-Induced Pulmonary Damage in Rats.

Maesa indica (Roxb.) Sweet is one of the well-known traditionally-used Indian plants. This plant is rich in secondary metabolites like phenolic acids, flavonoids, alkaloids, glycosides, saponins, and carbohydrates. It contains numerous therapeutically active compounds like palmitic acid, chrysophanol, glyceryl palmitate, stigmasterol, ß-sitosterol, dodecane, maesaquinone, quercetin 3-rhaminoside, rutin, chlorogenic acid, catechin, quercetin, nitrendipine, 2,3-dihydroxypropyl octadeca-9,12-dienoate, kiritiquinon, and ß-thujone. The Maesa indica plant has been reported to have many biological properties including antidiabetic, anticancer, anti-angiogenic, anti-leishmanial, antioxidant, radical scavenging, antibacterial, antiviral, and anti-coronavirus effects. One purpose of the current study was to investigate the leaves' metabolome via Triple-Time-of-Flight-Liquid-Chromatography-Mass Spectrometry (T-TOF LC/MS/MS) to identify the chemical constituents of the Maesa indica ethanolic extract (ME). Another purpose of this study was to explore the protective effect of ME against potassium dichromate (PD)-induced pulmonary damage in rats. Rats were assigned randomly into four experimental groups. Two different doses of the plant extract, (25 and 50 mg/kg), were administered orally for seven consecutive days before PD instillation injection. Results of our study revealed that ME enhanced cellular redox status as it decreased lipid peroxidation marker, MDA and elevated reduced glutathione (GSH). In addition, ME upregulated the cytoprotective signaling pathway PI3K/AKT. Moreover, ME administration ameliorated histopathological anomalies induced by PD. Several identified metabolites, such as chlorogenic acid, quercetin, apigenin, kaempferol, luteolin, and rutin, had previously indicated lung-protective effects, possibly through an antioxidant effect and inhibition of oxidative stress and inflammatory mediators. In conclusion, our results indicated that ME possesses lung-protective effects, which may be the result of its antioxidant and anti-inflammatory properties.

Metabolomic study of the estrogenic and anti-osteoporotic potential of Erythrina bidwillii leaf.

Erythrina bidwillii Lindl., Leguminosae, constitutes a valuable crop for horticulture and medicine; however, it is rarely investigated. Menopause is a crucial transitional period in women's health. Women worldwide consider the use of phytoestrogens as a safe hormone replacement therapy to alleviate detrimental menopausal symptoms. Thus, the discovery of novel phytoestrogens is highly demanded. The present study aimed to investigate, for the first time, the metabolomic profile and the estrogenic potential of E. bidwillii Lindl. leaf. Ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry and gas chromatography-mass spectrometry metabolite profiling revealed the prevalence of alkaloids, flavonoids, isoflavonoids and fatty acids. Additionally, five erythrinan alkaloids, cristanine A (1), 8-oxoerythraline (2), (+)-erythrinine (3), (+)-erythraline (4) and 8-oxoerythrinine (5), along with the isoflavonoid genistin (6), were isolated. Erythrina bidwillii leaf extract exhibited significant in vivo estrogenic, anti-osteoporotic, anti-hyperlipidemic, hepatoprotective, and nephroprotective activities, utilizing ovariectomized rat model. Moreover, ethyl acetate and hexane fractions possessed significant in vitro estrogeic potential on MCF-7 cell lines. An in silico study of the isolated metabolites revealed that (+)-erythrinine (3) and 8-oxoerythrinine (5) exhibited the highest affinity for ERα and ERß, respectively, modeling them as potential estrogenic lead metabolites. Therefore, E. bidwillii leaf could be employed as promising hormone replacement therapy for postmenopausal women after thorough clinical trials.

Magnetic targeting of lornoxicam/SPION bilosomes loaded in a thermosensitive in situ hydrogel system for the management of osteoarthritis: Optimization, in vitro, ex vivo, and in vivo studies in rat model via modulation of RANKL/OPG.

Osteoarthritis is a bone and joint condition characterized pathologically by articular cartilage degenerative damage and can develop into a devastating and permanently disabling disorder. This investigation aimed to formulate the anti-inflammatory drug lornoxicam (LOR) into bile salt-enriched vesicles loaded in an in situ forming hydrogel as a potential local treatment of osteoarthritis. This was achieved by formulating LOR-loaded bilosomes that are also loaded with superparamagnetic iron oxide nanoparticles (SPIONs) for intra-muscular (IM) administration to improve joint targeting and localization by applying an external magnet to the joint. A 31.22 full factorial design was employed to develop the bilosomal dispersions and the optimized formula including SPION (LSB) was loaded into a thermosensitive hydrogel. Moreover, in vivo evaluation revealed that the IM administration of LSB combined with the application of an external magnet to the joint reversed carrageen-induced suppression in motor activity and osteoprotegerin by significantly reducing the elevations in mitogen-activated protein kinases, extracellular signal-regulated kinase, and receptor activator of nuclear factor kappa beta/osteoprotegerin expressions. In addition, the histopathological evaluation of knee joint tissues showed a remarkable improvement in the injured joint tissues. The results proved that the developed LSB could be a promising IM drug delivery system for osteoarthritis management.

Immunoregulatory role of hesperidin against ovalbumin (OVA)-induced bronchial asthma and depression in rats.

Links between bronchial asthma and depression have recently become a great subject of interest. The present study was carried out to assess the protective role of hesperidin against ovalbumin (OVA)-induced bronchial asthma that is associated with depression in rats, for this purpose, four groups. Rats were sensitized with intraperitoneal administration of 200 µg OVA/10 mg aluminum hydroxide (Al (OH) 3 for 3 consecutive days then at day 11 followed by intranasal challenge with OVA (1.5 mg/kg) at days 19, 20, and 21. Rats were pretreated with hesperidin (100 & 200 mg/kg) 1h before OVA challenge. At the end of the study, behavioral tests, biochemical indices, and histopathological architectures of lung and brain tissues were evaluated. Our findings showed that hesperidin significantly ameliorated the reduction in motor activity, motor coordination, forced swimming, CD4, CD25 and foxp3, interleukin-10 (IL-10), dopamine, serotonin, and neurotrophin-3 (NT3) as well as alleviated the elevation in transforming growth factor-beta (TGF-ß), tumor necrosis factor-alpha (TNF-α), iL-5, and immunoglobulin E (IgE). In addition, hesperidin reduced cellular infiltration, alveolar sacs damage, the bronchioles wall disruption, and nuclei pyknosis in neuron cells. Finally, hesperidin may provide protection against OVA-induced asthma and depression. This impact could be mediated in part by its anti-inflammatory and immunoregulatory properties.

Explicit mechanistic insights of Prosopis juliflora extract in streptozotocin-induced diabetic rats at the molecular level.

Background: The Ancient system of medicine showed the limelight on the use of herbal remedies and was found to possess minimal side effects and acceptable therapeutic outcomes. In this context, Prosopis juliflora gained importance in managing chronic diseases such as cancer, dermatological diseases, and chronic inflammatory disorders. Hence, P. juliflora was selected for further investigation associated with diabetes and inflammation. Aim: The present study aimed to evaluate the anti-diabetic activity in chemically induced experimental rats and explore the nature of phytocomponents that may produce this activity. Methods: Experimentally, diabetes was induced by a single administration of streptozotocin at 50 mg/kg intraperitoneally in Wistar rats. The animals were treated orally with P. juliflora at low and high doses (200 and 400 mg/kg) for 10 days. Blood collected from the retro-orbital plexus was analyzed for parameters like blood glucose levels, insulin, adiponectin, Keap1 and Nrf2. PPAR-γ, AMPK and GLUT 2 levels were analyzed in the pancreatic tissue. Besides, at the end of the experiment, animals were sacrificed, and the pancreatic tissue sections were subjected for histopathological, morphometrical and immune histochemical exploration. The phytochemical composition of the plant was investigated by GC-MS. Results: The administration of P. juliflora higher dose showed a significant decrease (**p< 0.001) in blood glucose levels with a rise in adiponectin, PPARγ, Keap1, Nrf2, Glut 2, and AMPK significantly (**p< 0.001). The inflammatory cytokine TNFα was also estimated and was found to be lowered significantly (**p< 0.001) in test drug-treated animals. Furthermore, in the pancreatic tissue, the number of Islets, the area, and the number of ß-cells were improved significantly with the sub-chronic treatment of P. juliflora extract. The structure and function of ß-cells were also revamped. Conclusion: The study results demonstrated a significant effect of P. juliflora on glycemic status, inflammatory condition, and the architecture of pancreatic tissue. In the identification and isolation process by GC MS, it was noticed that P. juliflora contained few phytochemical constituents from which it might be considered a promising drug for type 2 diabetes mellitus.

Utilization of response surface design for development and optimization of rosuvastatin calcium-loaded nano-squarticles for hair growth stimulating VEGF and IGF production: in-vitro and in-vivo evaluation.

INTRODUCTION: Countless individuals experience negative emotions as hair loss pattern affects their self-esteem and well-being. Rosuvastatin calcium (Ca-RUV) was reported to stimulate the growth of the hair in the applied area, hence, it was selected as a potential hair loss treatment drug. SIGNIFICANCE: This study aims to develop and optimize (Ca-RUV) loaded squarticles (SQRs) and assess their ability to deliver and release Ca-RUV in the hair follicle for the promotion of hair growth. METHODS: A response surface design was utilized to study the effect of varying Pluronic® F68 (PF68) and the percentage of liquid lipids within the core of the SQRs and the effects of particle size, entrapment efficiency, and drug released percentage after 24 h (%Q24) were assessed. The optimized formula was subjected to DSC, XRD, and in-vivo evaluation in rats. RESULTS: SQRs stabilized by 0.8% PF68 and contained 37.5% liquid lipids showed an acceptable particle size (250 nm), drug entrapment efficiency (75%), and %Q24 (100%). The in-vivo studies illustrated the ability of the formula to regrow hair in animals after 10 days due to the elevation of the vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) to their normal values and by 9% and 54%, respectively, relative to standard therapy minoxidil (5%). CONCLUSION: Thus, it can be concluded that the optimized formula of Ca-RUV loaded SQRs showed superior in-vivo results in the promotion of hair growth in a shorter period relative to the marketed product. Therefore, the formula can offer a viable option for the treatment of hair loss.

Chondroitin Sulphate-Chitosan polyelectrolyte complexes for etorocoxib transdermal delivery: in silico, in vitro and in vivo studies.

Rheumatoid arthritis (RA) is a chronic autoimmune disease which affects around 1% globally leading to joint inflammation and disability. Etorocoxib (ETR) is a potent COX-2 inhibitor traditionally used orally to alleviate RA induced inflammation, yet it causes hepatic side effects on prolonged use. This study aims for in silico optimization of ETR polyelectrolyte complex (PEC) utilizing chondroitin sulphate (CS) and chitosan (CH) for transdermal delivery to RA-inflamed joints with a synergistic anti-inflammatory action owing to CS. An artificial neural network (ANN) combined with 22 factorial design was used to optimize the PEC formula according to particle size (PS) and entrapment efficiency (%EE) by varying CS and CH concentrations. The optimum ETR PEC was incorporated in a gel and examined for its in vitro release, ex vivo permeation, in vivo inflammatory biomarkers, and histopathological evaluation in rats. The optimized formula (F3) with 0.1 CH% w/w and 0.5 CS %w/w showed a PS of 214.98 ± 17.24 nm, %EE 75.31 ± 1.67%, and enhanced in vitro release profile, ex vivo permeation and in vivo anti-inflammatory effect compared to ETR gel via suppressing the expression of IL-6, TNF-α, and TGF-ß pro-inflammatory cytokines as well as the additional anti-inflammatory effect of CS. In conclusion, ETR-PEC gel holds promise as transdermal therapy for managing RA-induced inflammation.

Coating with tripolyphosphate-crosslinked chitosan as a novel approach for enhanced stability of emulsomes following oral administration: Rutin as a model drug with improved anti-hyperlipidemic effect in rats.

The aim of the current study is to preserve the emulsomal vesicles against the harsh condition of gastrointestinal tract (GIT), after oral administration, employing tripolyphosphate (TPP)-crosslinked chitosan as a protective coating layer. Rutin was used as a model drug with evaluation of anti-hyperlipidemic activity in rats. The rutin loaded unmodified emulsomes were prepared using tripalmitin and soybean phosphatidylcholine (SPC), by thin film method. Drug loading for the prepared formulations ranged between 6.80 and 15.50 %. The selected formulation (RT-Emuls-6) comprised tripalmitin and SPC, molar ratio 1:1, and exhibited particle size (PS) and zeta potential (ZP) of 150.40 nm and -35.35 mV, respectively. RT-Emuls-6 was then modified by coating with either solely chitosan (RT-Emuls-6-Ch) or TPP-crosslinked chitosan (RT-Emuls-6-Ch-TPP-1). The latter exhibited PS and ZP values of 269.60 nm and 37.17 mV, respectively. Transmission electron microscopy of RT-Emuls-6-Ch-TPP-1 showed a dense pale greyish layer of a coating layer of chitosan crosslinked with TPP surrounding SPC bilayers. Fourier transform infrared spectroscopy analysis along with X-ray powder diffraction confirmed cross-linking between chitosan and TPP. Stability study in the simulated GIT fluids revealed that the order of rutin retained percentage was RT-Emuls-6-Ch-TPP-1 > RT-Emuls-6-Ch > RT-Emuls-6 (80.02, 50.66 and 44.41 %, respectively for simulated gastric fluid and 63.50, 55.66 and 24.00 %, respectively for simulated intestinal fluid, after 2 h incubation). Anti-hyperlipidemic activity of rutin loaded emulsomes was evaluated, after oral administration, in a high fat diet-induced hyperlipidemia in rats. The order of activity was as follows: RT-Emuls-6-Ch-TPP-1 > RT-Emuls-6-Ch > RT-Emuls-6 > free rutin. These findings revealed the potential of TPP-crosslinked chitosan as a protective coating layer for enhancing the stability of emulsomes against the harsh condition of GIT. RT-Emuls-6-Ch-TPP-1 had a potent anti-hyperlipidemic activity via regulation of lipids, oxidative stress, irisin and uncoupling protein 1.

Synergistic effect of arginine and Lactobacillus plantarum against potassium dichromate induced-acute liver and kidney injury in rats: Role of iNOS and TLR4/NF-κB signaling pathways.

Objectives: Our study was conducted to evaluate the synergistic effect of arginine (ARG) and Lactobacillus plantarum against potassium dichromate (K2Cr2O7) induced-acute hepatic and kidney injury. Materials and Methods: Fifty male Wistar rats were divided into five groups. The control group received distilled water. The potassium dichromate group (PDC) received a single dose of PDC (20 mg/kg; SC). The arginine group (ARG) and Lactobacillus plantarum group received either daily doses of ARG (100 mg/kg, PO) or L. plantarum (109 CFU/ml, PO) for 14 days. The combination group (ARG+L. plantarum) received daily doses of ARG (100 mg/kg) with L. plantarum (109 CFU/ml), orally for 14 days, before induction of acute liver and kidney injury. Forty eight hours after the last dose of PDC, serum biochemical indices, oxidative stress biomarkers, pro-inflammatory cytokines, histopathological and immunohistochemical analysis were evaluated. Results: Combining ARG with L. plantarum restored the levels of serum hepatic & kidney enzymes, hepatic & renal oxidative stress biomarkers, and TLR 4/ NF-κB signaling pathway. Furthermore, they succeeded in decreasing the expression of iNOS and ameliorate the hepatic and renal markers of apoptosis: Caspase-3, Bax, and Bcl2. Conclusion: This study depicts that combining ARG with L. plantarum exerted a new bacteriotherapy against hepatic and renal injury caused by PDC.

Topical caffeine-loaded nanostructured lipid carriers for enhanced treatment of cellulite: A 32 full factorial design optimization and in vivo evaluation in rats.

The goal of this study was the development and evaluation of semisolid caffeine (CAF) loaded nanostructured lipid carriers (NLCs) for topical treatment of cellulite. CAF-loaded NLC formulations were prepared via high-speed homogenization followed by ultrasonication. A 32 full factorial design was employed for formulation optimization. The total lipid content (%) and the liquid lipid content per total lipids (%) were chosen as factors, whereas particle size (PS), polydispersity index (PDI), zeta potential (|ZP|) and viscosity (VIS) were selected as responses. The design suggested CAF-NLC3 as the optimum formulation consisting of a total lipid content of 15% w/w (palmitic acid and soft paraffin/isopropyl myristate, 7:3 w/w) and a surfactant content of 10% w/w (Tween 80/lecithin, 8:1.2 w/w). CAF-NLC3 revealed PS, PDI, ZP, VIS and CAF content values of 318.8 nm, 0.253, -41.1 mV, 18.0 Pa.s and 97.57%, respectively. It showed a pseudoplastic rheological behavior, acceptable pH value (5.25), good spreadability (1.12 mm2/g) and spherical shape employing transmission electron microscopy. Differential scanning calorimetry and X-ray diffraction demonstrated the amorphization of CAF in CAF-NLC3. CAF-NLC3 remained stable for 3 months at room and refrigeration conditions. A single topical application of CAF-NLC3 on shaved abdominal skins of Wistar rats revealed enhanced skin retention of CAF by 2-fold and 1.4-fold after 4 h when compared with plain CAF gel (CAF-P) and marketed CAF gel (CAF-M), respectively. Furthermore, CAF-NLC3 exhibited a superior anti-cellulite activity in comparison with CAF-P and CAF-M through elevating extracellular matrix components (collagen 1, elastin and hyaluronic acid) and stimulating the brown adipose tissue thermogenesis via up-regulating UCP1 and PPAR-γ expression. In addition, CAF-NLC3 prominently increased lipolysis through HSL activity and decreased pro-inflammatory cytokines such as ICAM-1 and VCAM-1 after 30 days of treatment on a high fat diet-induced cellulite rat model. These findings were further confirmed by histopathological examination supported by morphometric analysis. Therefore, incorporation of CAF in a semisolid NLC formulation would be a promising cosmetic approach for the topical treatment of cellulite.

Cold plasma approach fortifies the topical application of thymoquinone intended for wound healing via up-regulating the levels of TGF-ß, VEGF, and α-SMA in rats.

Wound healing is a series of coordinated events that involve tissue repair and regeneration. Cold atmospheric plasma approach sheds the light on the mechanism that initiates the inflammatory responses throughout the healing cascade. The present study was planned to assess the effect of thymoquinone treated with cold plasma (TQcp) on the rat wound model compared to thymoquinone (TQ). To assess the wound healing potential of TQcp, a full-thickness wound model was used. The induced wound was smeared, starting just after excision, twice daily with TQcp and TQ for 7 days. Our findings revealed that TQcp improved the skin healing potential by augmenting the skin regeneration indices as evidenced by enhancing the new production of hyaluronic acid and collagen type I. TQcp significantly reduced the skin content of tumor necrosis factor- α and inhibited the hypertrophic scarring by up-regulating the skin content of transforming growth factor-beta. Furthermore, TQcp enhanced the levels of interleukin-10, alpha smooth muscle actin and vascular endothelial growth factor, demonstrating a great potential for wound healing that also reflected in the histopathological and ultra-structural picture of the skin. Finally, our results demonstrated that TQcp revealed a significant potential for wound healing than TQ alone.

Modeling and in-vivo evaluation of fibrinolytic enzyme produced by Bacillus subtilis Egy under solid state fermentation.

Blood clot formation increases cases of myocardial infarction (AMI) and stroke, thus urges directing much research works for treatment and prevention of the causes. One of these directions is the microbial production of fibrinolytic enzymes as thrombolytic agents. In the current work, Bacillus subtilis Egy has been used for enzyme production under solid state fermentation. Among twelve nutrient meals in addition to wheat bran as a control fodder yeast yielded the highest enzyme activity reaching 114U/g. Applying statistical model for optimization of enzyme production revealed that 3.6%, fodder yeast; 40%, moisture content; 6 days, incubation period and 2%, inoculum size were the optimum conditions for maximum fibrinolytic enzyme production (141.02 U/g) by Bacillus subtilis Egy under solid-state fermentation The model was significant and data were experimentally validated. The produced fibrinolytic enzyme was evaluated for in vitro and in vivo cytotoxicity. In-vivo examination of the enzyme resulted in no mortality during the first 24 h after treatment. After 14 days, the results revealed no significant changes detected in hematological parameters (RBCs, MCV, hemoglobin except WBCs which showed an increase for both sexes. Histopathological examination of liver and kidney of rats received oral and subcutaneous treatments showed normal architecture. The data showed the applicability of the produced enzyme for the treatment of blood clot with no significant effect on living cells or on physiological functions.

Reliability of assessing morphologic features with prognostic significance in cytology specimens of epithelioid diffuse pleural mesothelioma and implications for cytopathology reporting.

BACKGROUND: The World Health Organization incorporates morphologic features with prognostic significance in the 2021 classification of epithelioid diffuse pleural mesothelioma (E-DPM). Although cytology specimens are often the first and occasionally the only specimen available for patients with DPM, these features have not yet been investigated in cytology. METHODS: Nuclear atypia, pleomorphic features, necrosis, and architectural patterns were retrospectively assessed in 35 paired cytology and concurrent/consecutive surgical pathology specimens of E-DPM. Agreement between pairs was determined via unweighted κ scores. Discordant cases were re-reviewed to determine the reasons for disagreement. RESULTS: Interpretation of nuclear atypia in cytology was concordant with histology in all cases (κ = 1.000; p < .001). The presence of pleomorphic features and necrosis was concordant in 97.1% (κ = 0.842; p < .001) and 85.7% (κ = 0.481; p = .001) of paired cases, respectively. Assessment of architectural patterns in cytology showed only slight agreement with histology (κ = 0.127; p = .037). In cytology cases (n = 23) with cell block material available, assessment of nuclear atypia and the presence of pleomorphic features showed perfect agreement (κ = 1.000; p < .001, each), the presence of necrosis showed moderate agreement (κ = 0.465; p = .008), and assessment of architectural patterns showed slight agreement (κ = 0.162; p = .15) in paired specimens. Most disagreements were due to sampling differences between cytology and histology specimens. CONCLUSIONS: Although complete nuclear grading of E-DPM is not possible given the unreliability of mitotic counts in cytology, assessment of nuclear atypia in cytology specimens is shown to be reliable. Identification of pleomorphic features and necrosis is also reliable despite occasional sampling issues. Assessment of architectural patterns is more limited in cytology.

Cubosome-based thermosensitive in situ gelling system for intranasal administration of lamotrigine with enhanced antiepileptic efficacy.

Lamotrigine (LTG) is a second-generation antiepileptic drug that belongs to Biopharmaceutics Classification System (BCS) class II. LTG has a low probability of crossing the BBB if administered orally. This study was designed to fabricate LTG cubosomal dispersion that is further loaded in a thermosensitive in situ gel to increase nasal residence time and enhance drug absorption across the nasal mucosal membrane. LTG-loaded cubosomes exhibited an entrapment efficiency ranging from 24.83% to 60.13%, a particle size ranging from 116.2 to 197.6 nm, and a zeta potential ≤-25.5 mV. The selected LTG-loaded cubosomal formulation was loaded in a thermosensitive in situ gel (cubogel) employing different concentrations of poloxamer 407. In vitro release study revealed sustained drug release from cubosomal and cubogel compared with free drug suspension. In vivo studies revealed enhanced antiepileptic efficacy of LTG cubogel and LTG cubosomes compared with free drug in rats with pilocarpine-induced epilepsy by stimulating the release of gamma-aminobutyric acid (GABA), total antioxidant capacity (TAC), and serotonin and by inhibiting the release of Ca2+, dopamine, acetylcholine (Ach), C-reactive protein (CRP), and glial fibrillary acidic protein (GFAP). LTG cubogel exhibited superior activity over LTG cubosomes. These findings reveal that the developed cubosomal thermosensitive in situ gel can enhance the antiepileptic efficacy of LTG via the intranasal route.

Natural ß-carotene prevents acute lung injury induced by cyclophosphamide in mice.

IL-17 is associated with varied inflammatory and immune-related diseases. However, the biological function of IL-17 and its expression in acute lung damage are not entirely known. Thanks to the powerful antioxidant properties of ß-carotene, we presumed that it would show a potent protecting effect against cyclophosphamide (CP) -induced acute lung injury (ALI) in mice. We studied the mechanisms underlying the effect of ß-carotene supplementation against CP-induced ALI in mice. We isolated the ß-carotene from Scenedesmus obliquus microalgae n-hexane extract and identified it by HPLC and 1H-NMR analysis. Within the experiments, 40 mice were assigned into five groups randomly: Group 1 (Control): Mice received saline. Group 2 (ß-carotene control): Mice were administered ß-carotene (40 mg/kg; orally) once daily for 10 sequent days without CP injection. Group 3 (CP): One i.p injection of 200 (mg/kg) of CP was given to mice. Group 4 and 5 (CP + ß-carotene): Mice were administered ß-carotene (20 and 40 mg/kg; orally) once a day for ten days following the CP injection. Lung samples were collected for lab analysis, after scarifying the animals at the experiment end. Administration of ß-carotene orally reduced CP-induced ALI and inflammation. ß-carotene significantly decreased wet-to-dry weight ratios (W/D), down-regulated IL-17, NF-κB, and IKBKB, decreased the contents of TNF-α, COX-2, and PKC, and increased the contents of SIRT1 and PPARγ in the lung tissues. ß-carotene ameliorated the histopathological changes induced by CP and reduced the scoring number of inflammatory cell infiltration and emphysema when compared to CP. Consequently, we conclude natural ß-carotene is a promising anti-inflammatory mediator for different inflammatory-related complications.