Spectrofluorometric determination of ascorbic acid in the plasma matrix: Exploring correlation with autism spectrum disorder.

Ascorbic acid (Vitamin C) is crucial for bodily functions, including collagen synthesis, immune system support and antioxidant defense. Despite autism spectrum disorder's multifactorial nature involving genetic, environmental and neurological factors, robust evidence exploring the association between ascorbic acid and this disorder is notably lacking. This study introduces an innovative spectrofluorometric method to quantify ascorbic acid in the plasma of healthy children and those with autism spectrum disorder. The method relies on the interaction of ascorbic acid with the fluorescent dye propidium iodide. In acidic conditions, propidium iodide undergoes protonation and selectively binds to the negatively charged ascorbic acid forming an ion-pair complex. This complex alters the molecular structure of propidium iodide inducing chemical fluorescence quenching, that can be utilized for ascorbic acid quantification. The developed method undergoes rigorous validation following ICH guidelines, demonstrating a linear relationship within a concentration range of 4-40 µg/mL, with high precision and accuracy metrics. Analysis of real plasma samples from autistic and healthy children reveals clinically and statistically elevated levels of ascorbic acid in those with autism spectrum disorder.

Antibiotics efficacy in clinical and microbiological cure of uncomplicated urinary tract infection: a systematic review and network meta-analysis.

PURPOSE: Fosfomycin has been used more frequently in managing uncomplicated urinary tract infections (UTIs) due to decreased compliance and increased multidrug-resistant bacteria. The aim of this network meta-analysis was to assess the efficacy of Fosfomycin compared to Nitrofurantoin, Trimethoprim-Sulfamethoxazole (TMP-SMX), and Ciprofloxacin in terms of clinical and microbiological cure alongside with other measurements. MATERIALS AND METHODS: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL). We included randomized control trials (RCTs) with uncomplicated UTI patients who received Fosfomycin, Nitrofurantoin, TMP-SMX, or Ciprofloxacin and reported the clinical or microbiological cure. We used Cochrane Risk of Bias Assessment Tool to assess the included studies' quality. R-software was used for all statistical analysis. We ranked all antibiotics using the netrank function which yielded P scores. Frequentist network meta-analysis was used to assess the efficacy of all outcomes. RESULTS: We included 13 RCTs with a total number of 3856 patients that showed Fosfomycin ranked the highest among the other antibiotics with respect to clinical cure (P-score = 0.99) and microbiological cure (P-score = 0.99) while Ciprofloxacin ranked the lowest (P-score = 0.11 and 0.02, respectively). Moreover, Ciprofloxacin yielded the highest relapse rate (P-score = 1), whereas TMP-SMX had the lowest relapse rate (P-score = 0.07). As for the adverse events, Ciprofloxacin demonstrated the highest adverse events as opposed to Fosfomycin (P-score = 0.98 and 0.05, respectively). CONCLUSION: The network meta-analysis demonstrated that Fosfomycin is the most effective antibiotic in treating uncomplicated UTIs with respect to clinical cure, microbiological cure, and adverse events profile.

Efficacy of forskolin as a promising therapy for chronic olfactory dysfunction post COVID-19.

PURPOSE: Olfactory dysfunction is increasingly common among COVID-19 patients, impacting their well-being. Reports have demonstrated decreased levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate among patients with chronic olfactory dysfunction. A prospective randomized clinical trial was developed to demonstrate the efficacy of an oral forskolin regimen treatment, an adenylyl cyclase activator that raises intracellular levels of cyclic adenosine monophosphate, for the treatment of olfactory dysfunction following COVID-19, compared to placebo regimen. METHODS: The study enrolled 285 participants with persistent olfactory dysfunction post COVID-19 infection, randomly assigning them to receive either placebo capsules (n = 120) or oral forskolin capsules (n = 165). Follow-up was conducted to track progress, with 18 participants from the placebo group and 12 from the forskolin group lost during this period. Olfactory function was assessed using the "Sniffin' Sticks" test, measuring threshold, discrimination and identification scores before and after treatment. RESULTS: Subjects administered forskolin capsules demonstrated a significant enhancement in their composite TDI (threshold, discrimination and identification) score, suggesting a notable amelioration in olfactory functionality. Moreover, the discrimination and identification scores notably improved within the forskolin group. Conversely, no significant alterations were observed in the threshold scores. CONCLUSION: This study suggests that forskolin can contribute potentially to improve chronic olfactory dysfunction post COVID-19. TRIAL REGISTRATION: DFM-IRB00012367-23-10-001.

Phosphoinositide 3-Kinase Inhibitors from Gladiolus segetum Ker-Gawl Corms Supported by Network Pharmacology.

Gladiolus segetum Ker-Gawl corms total extract exhibited remarkable in vitro anti-proliferative effects against panel of cancer cell lines; including human colon carcinoma (Caco-2), human breast cancer (MCF7) and hepatocellular carcinoma (HepG2) cell lines with IC50 values of 7.4, 9.1 and 11.2 µg/ml, respectively. The total ethanolic extract of G. segetum Ker-Gawl corms was subjected to untargeted metabolomics profiling using LC-HR-ESI-MS, which revealed the presence of various clusters of phytoconstituents as triterpenes, anthraquinones, flavonoids and phenolic derivatives. Network pharmacology study was performed for all identified compounds, the formed networks identified 73 intersected genes. The diagrammatic illustration of the top pathways revealed that phosphoinositide 3-kinase (PI3K) gene is the effective dominant gene in the top four KEGG pathways. Upon molecular docking and molecular dynamics investigation, kaempferol-3-O-glucopyranoside was suggested to be key anticancer metabolite. Interestingly, cytotoxic investigation of this compound revealed potential activity against the tested cancer cell lines (Caco-2, MCF7 and HepG2) with IC50 values of 6.2, 8.5 and 9.3 µg/ml, respectively. The present study highlighted the potential of G. segetum Ker-Gawl as a promising source of interesting anticancer scaffolds.

Network Pharmacological Analysis of the Red Sea Sponge Hyrtios erectus Extract to Reveal Anticancer Efficacy of Corresponding Loaded Niosomes.

In this study, the LC-HRMS-assisted chemical profiling of Hyrtios erectus sponge led to the annotation of eleven major compounds (1-11). H. erectus-derived crude extract (HE) was tested in vitro for its antiproliferative activity against three human cancer cell lines, Hep-G2 (human liver cancer cell line), MCF-7 (breast cancer cell line), and Caco-2 (colon cancer cell line), before and after encapsulation within niosomes. Hyrtios erectus extract showed moderate in vitro antiproliferative activities towards the studied cell lines with IC50 values 18.5 ± 0.08, 15.2 ± 0.11, and 13.4 ± 0.12, respectively. The formulated extract-containing niosomes (size 142.3 ± 10.3 nm, PDI 0.279, and zeta potential 22.8 ± 1.6) increased the in vitro antiproliferative activity of the entrapped extract significantly (IC50 8.5 ± 0.04, 4.1 ± 0.07, and 3.4 ± 0.05, respectively). A subsequent computational chemical study was performed to build a sponge-metabolite-targets-cancer diseases network, by focusing on targets that possess anticancer activity toward the three cancer types: breast, colon, and liver. Pubchem, BindingDB, and DisGenet databases were used to build the network. Shinygo and KEGG databases in addition to FunRich software were used for gene ontology and functional analysis. The computational analysis linked the metabolites to 200 genes among which 147 genes related to cancer and only 64 genes are intersected in the three cancer types. The study proved that the co-occurrence of compounds 1, 2, 3, 7, 8, and 10 are the most probable compounds possessing cytotoxic activity due to large number of connections to the intersected cytotoxic genes with edges range from 9-14. The targets possess the anticancer effect through Pathways in cancer, Endocrine resistance and Proteoglycans in cancer as mentioned by KEGG and ShinyGo 7.1 databases. This study introduces niosomes as a promising strategy to promote the cytotoxic potential of H. erectus extract.

Anti-Inflammatory and Antioxidant Properties of Malapterurus electricus Skin Fish Methanolic Extract in Arthritic Rats: Therapeutic and Protective Effects.

The protective and therapeutic anti-inflammatory and antioxidant potency of Malapterurus electricus (F. Malapteruridae) skin fish methanolic extract (FE) (300 mg/kg.b.wt/day for 7 days, orally) was tested in monosodium urate(MSU)-induced arthritic Wistar albino male rats' joints. Serum uric acid, TNF-α, IL-1ß, NF-𝜅B, MDA, GSH, catalase, SOD, and glutathione reductase levels were all measured. According to the findings, FE significantly reduced uric acid levels and ankle swelling in both protective and therapeutic groups. Furthermore, it has anti-inflammatory effects by downregulating inflammatory cytokines, primarily through decreased oxidative stress and increased antioxidant status. All the aforementioned lesions were significantly improved in protected and treated rats with FE, according to histopathological findings. iNOS immunostaining revealed that protected and treated arthritic rats with FE had weak positive immune-reactive cells. Phytochemical analysis revealed that FE was high in fatty and amino acids. The most abundant compounds were vaccenic (24.52%), 9-octadecenoic (11.66%), palmitic (34.66%), stearic acids (14.63%), glycine (0.813 mg/100 mg), and alanine (1.645 mg/100 mg). Extensive molecular modelling and dynamics simulation experiments revealed that compound 4 has the potential to target and inhibit COX isoforms with a higher affinity for COX-2. As a result, we contend that FE could be a promising protective and therapeutic option for arthritis, aiding in the prevention and progression of this chronic inflammatory disease.

New Halogenated Compounds from Halimeda macroloba Seaweed with Potential Inhibitory Activity against Malaria.

Malaria is one of the most important infectious diseases worldwide. The causative of the most severe forms of malaria, Plasmodium falciparum, has developed resistances against all the available antimalarial drugs. In the present study, the phytochemical investigation of the green seaweed Halimeda macroloba has afforded two new compounds 1-2, along with 4 known ones 3-6. The structures of the compounds had been confirmed using 1& 2D-NMR and HRESIMS analyses. Extensive machine-learning-supported virtual-screening suggested cytochrome-C enzyme as a potential target for compound 2. Docking, absolute-binding-free-energy (ΔGbinding) and molecular-dynamics-simulation (MDS) of compound 2 revealed the strong binding interaction of this compound with cytochrome-C. In vitro testing for crude extract and isolated compounds revealed the potential in vitro inhibitory activity of both extract and compound 2 against P. falciparum. The crude extract was able to inhibit the parasite growth with an IC50 value of 1.8 ± 0.35 µg/mL. Compound 2 also showed good inhibitory activity with an IC50 value of 3.2 ± 0.23 µg/mL. Meanwhile, compound 6 showed moderate inhibitory activity with an IC50 value of 19.3 ± 0.51 µg/mL. Accordingly, the scaffold of compound 2 can be considered as a good lead compound for the future development of new antimalarial agents.

Wound Healing Metabolites from Peters' Elephant-Nose Fish Oil: An In Vivo Investigation Supported by In Vitro and In Silico Studies.

Gnathonemuspetersii (F. Mormyridae) commonly known as Peters' elephant-nose fish is a freshwater elephant fish native to West and Central African rivers. The present research aimed at metabolic profiling of its derived crude oil via GC-MS analysis. In addition, wound healing aptitude in adult male New Zealand Dutch strain albino rabbits along with isolated bioactive compounds in comparison with a commercial product (Mebo®). The molecular mechanism was studied through a number of in vitro investigations, i.e., radical scavenging and inhibition of COX enzymes, in addition to in silico molecular docking study. The results revealed a total of 35 identified (71.11%) compounds in the fish oil, belonging to fatty acids (59.57%), sterols (6.11%), and alkanes (5.43%). Phytochemical investigation of the crude oil afforded isolation of six compounds 1-6. Moreover, the crude oil showed significant in vitro hydrogen peroxide and superoxide radical scavenging activities. Furthermore, the crude oil along with one of its major components (compound 4) exhibited selective inhibitory activity towards COX-2 with IC50 values of 15.27 and 2.41 µM, respectively. Topical application of the crude oil on excision wounds showed a significant (p < 0.05) increase in the wound healing rate in comparison to the untreated and Mebo®-treated groups, where fish oil increased the TGF-ß1 expression, down-regulated TNF-α, and IL-1ß. Accordingly, Peters' elephant-nose fish oil may be a potential alternative medication helping wound healing owing to its antioxidant and anti-inflammatory activities.

Evaluation of microalgae and cyanobacteria as potential sources of antimicrobial compounds.

In recent decades, marine microorganisms have become known for their ability to produce a wide variety of secondary bioactive metabolites. Several compounds have been isolated from marine microorganisms for the development of novel bioactives for the food and pharmaceutical industries. In this study, a number of microalgae were evaluated for their antimicrobial activity against gram-positive and gram-negative bacteria, including food and plant pathogens, using various extraction techniques and antimicrobial assays. Disc diffusion and spot-on-lawn assays were conducted to confirm the antimicrobial activity. To measure the potency of the extracts, minimum inhibition concentrations (MIultCs) were measured. Three microalgae, namely Isochrysis galbana, Scenedesmus sp. NT8c, and Chlorella sp. FN1, showed strong inhibitory activity preferentially against gram-positive bacteria. These microalgal species were then selected for further purification and analysis, leading to compound identification. By using a mixture of different chromatography techniques gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS), we were able to separate and identify the dominant compounds that are responsible for the inhibitory activity. Additionally, nuclear magnetic resonance (NMR) was used to confirm the presence of these compounds. The dominant compounds that were identified and purified in the extracts are linoleic acid, oleic acid, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). These compounds are the potential candidates that inhibit the growth of gram-positive bacteria. This indicates the potential use of microalgae and their antimicrobial compounds as biocontrol agents against food and plant pathogens.

Unraveling potential neuroprotective mechanisms of herbal medicine for Alzheimer's diseases through comprehensive molecular docking analyses.

Alzheimer's disease (AD) continues to be a worldwide health concern, demanding innovative therapeutic approaches. This study investigates the neuroprotective potential of herbal compounds by scrutinizing their interactions with Beta-Secretase-1 (BACE1). Through comprehensive molecular docking analyses, three compounds, Masticadienonic acid (ΔG: -9.6 kcal/mol), Hederagenin (ΔG: -9.3 kcal/mol), and Anthocyanins (ΔG: -8.1 kcal/mol), emerge as promising BACE1 ligands, displaying low binding energies and strong affinities. ADME parameter predictions, drug-likeness assessments, and toxicity analyses reveal favorable pharmacokinetic profiles for these compounds. Notably, Masticadienonic Acid exhibits optimal drug-likeness (-3.3736) and negligible toxicity concerns. Hederagenin (drug-likeness: -5.3272) and Anthocyanins (drug-likeness: -6.2041) also demonstrate promising safety profiles. Furthermore, pharmacophore modeling elucidates the compounds' unique interaction landscapes within BACE1's active site. Masticadienonic acid showcases seven hydrophobic interactions and a hydrogen bond acceptor interaction with Thr232. Hederagenin exhibits a specific hydrogen bond acceptor interaction with Trp76, emphasizing its selective binding. Anthocyanins reveal a multifaceted engagement, combining hydrophobic contacts and hydrogen bond interactions with key residues. In conclusion, Masticadienonic acid, Hederagenin, and Anthocyanins stand out as promising candidates for further experimental validation, presenting a synergistic balance of efficacy and safety in combating AD through BACE1 inhibition.

Successful manual detorsion of testicular torsion in an elderly patient: A case report.

INTRODUCTION: Testicular torsions in elderly individuals are rare occurrences that are often managed surgically. CASE PRESENTATION: We present the first reported case of a successful manual detorsion in a 70-year-old male patient, resulting in clinical and radiological improvement. CLINICAL DISCUSSION: In this case report we discuss the role of manual detorsion alone in elderly without the need for surgery. CONCLUSION: Observation of our patient for 24 h post-detorsion ensured stability before discharge.

In vitro Assessment of the Antimicrobial Properties of Orthodontic Bonding Materials.

Background: Orthodontic bonding materials are extensively used in dentistry, but their antimicrobial properties are of growing concern due to the risk of biofilm formation and associated complications. Understanding the antimicrobial efficacy of these materials is crucial for maintaining oral health during orthodontic treatment. Materials and Methods: In this in vitro study, we evaluated the antimicrobial properties of various orthodontic bonding materials against common oral pathogens. Samples of bonding materials were prepared and exposed to microbial strains including Streptococcus mutans, Porphyromonas gingivalis, and Candida albicans. Antimicrobial activity was assessed using agar diffusion assays and microbial viability assays. Results: The tested orthodontic bonding materials exhibited varying degrees of antimicrobial activity. Material A showed a zone of inhibition of 12 mm against S. mutans, 8 mm against P. gingivalis, and 6 mm against C. albicans. Material B exhibited slightly higher antimicrobial activity with inhibition zones of 14 mm, 10 mm, and 8 mm against S. mutans, P. gingivalis, and C. albicans, respectively. Material C displayed the highest antimicrobial activity, with inhibition zones of 16 mm against S. mutans, 12 mm against P. gingivalis, and 10 mm against C. albicans. Microbial viability assays confirmed the efficacy of these materials in reducing microbial growth. Conclusion: Our findings demonstrate that orthodontic bonding materials possess varying degrees of antimicrobial properties. Material C exhibited the highest efficacy against the tested microbial strains. Incorporating antimicrobial agents into orthodontic bonding materials may contribute to the prevention of oral infections during orthodontic treatment.

Comparative Analysis of the Frictional Resistance of Various Archwire-Ligature Combinations in Orthodontics.

Background: Frictional resistance is a critical factor influencing the efficacy of orthodontic treatment. Archwire-ligature combinations play a significant role in determining frictional forces within the orthodontic system. This study aimed to conduct a comparative analysis of the frictional resistance exhibited by various archwire-ligature combinations commonly used in orthodontics. Materials and Methods: A total of five archwire-ligature combinations were evaluated in this study: stainless steel archwire with elastic ligatures, stainless steel archwire with metal ligatures, nickel-titanium archwire with elastic ligatures, nickel-titanium archwire with metal ligatures, and beta-titanium archwire with metal ligatures. Frictional resistance was measured using a universal testing machine under standardized conditions, with a constant load applied to simulate clinical conditions. Results: The frictional resistance varied significantly among the different archwire-ligature combinations. The mean frictional resistance values (in arbitrary units) recorded were as follows: stainless steel archwire with elastic ligatures (X), stainless steel archwire with metal ligatures (Y), nickel-titanium archwire with elastic ligatures (Z), nickel-titanium archwire with metal ligatures (A), and beta-titanium archwire with metal ligatures (B). Statistical analysis revealed that combination A exhibited the lowest frictional resistance, followed by combination B, combination Z, combination X, and combination Y. Conclusion: The choice of archwire-ligature combination significantly affects the frictional resistance within the orthodontic system. Nickel-titanium archwires combined with metal ligatures demonstrated lower frictional resistance compared with stainless steel archwires, regardless of the ligature type. Among the combinations tested, nickel-titanium archwire with metal ligatures exhibited the lowest frictional resistance, suggesting its potential for reducing friction and improving treatment efficiency in orthodontic practice.

Spectrofluorimetric determination of vitamin D in the serum of autistic and healthy children using functionalized graphene quantum dots.

Vitamin D is one of the most essential nutrients for brain development, and deficiencies during pregnancy and early childhood development might be associated with autism. Regular monitoring of serum 25-hydroxyvitamin D3 level could help in early diagnosis and therapy. Analytical measurement of serum 25-hydroxyvitamin D3 level using the traditional matrix-matched calibration technique yields inaccurate results due to absence of serum matrix free from 25-hydroxyvitamin D3. The aim of this work was to develop a validated spectrofluorimetric methodology based on the standard addition approach for quantifying 25-hydroxyvitamin D3 levels in real serum samples of autistic children. The spectrofluorimetric methodology utilizes functionalized graphene quantum dots as a fluorescent probe for selective quantification of 25-hydroxyvitamin D3 level, which is based on measuring the quenching properties of 25-hydroxyvitamin D3 on a fluorescent probe. The standard addition approach exhibits a minimal matrix interference since it identically utilizes the same matrix of each study sample for creating its own calibration curve. The method was validated using the guidelines outlined in ICH M10 draft for endogenous compounds quantification. The method was successfully applied for quantifying the serum 25-hydroxyvitamin D3 levels in autistic and healthy children, and autistic children had significantly lower serum 25-hydroxyvitamin D3 levels (with a mean ± SD of 23.80 ± 17.19) when compared to healthy children (with a mean ± SD of 50.13 ± 18.74, P < 0.001). These results suggested an association between vitamin D deficiency and autism.

Cytotoxic metabolites from Sinularia levi supported by network pharmacology.

The in-vitro anti-proliferative evaluation of Sinularia levi total extract against three cell lines revealed its potent effect against Caco-2 cell line with IC50 3.3 µg/mL, followed by MCF-7 and HepG-2 with IC50 6.4 µg/mL and 8.5 µg/mL, respectively, in comparison to doxorubicin. Metabolic profiling of S. levi total extract using liquid chromatography coupled with high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS) revealed the presence of phytoconstituents clusters consisting mainly of steroids and terpenoids (1-20), together with five metabolites 21-25, which were additionally isolated and identified through the phytochemical investigation of S. levi total extract through various chromatographic and spectroscopic techniques. The isolated metabolites included one sesquiterpene, two steroids and two diterpenes, among which compounds prostantherol (21) and 12-hydroperoxylsarcoph-10-ene (25) were reported for the first time in Sinularia genus. The cytotoxic potential evaluation of the isolated compounds revealed variable cytotoxic effects against the three tested cell lines. Compound 25 was the most potent with IC50 value of 2.13 ± 0.09, 3.54 ± 0.07 and 5.67 ± 0.08 µg/mL against HepG-2, MCF-7 and Caco-2, respectively, followed by gorgosterol (23) and sarcophine (24). Additionally, network analysis showed that cyclin-dependent kinase 1 (CDK1) was encountered in the mechanism of action of the three cancer types. Molecular docking analysis revealed that CDK1 inhibition could possibly be the reason for the cytotoxic potential.

Expression of concern: The anti-Alzheimer potential of Tamarindus indica: an in vivo investigation supported by in vitro and in silico approaches.

Expression of concern for 'The anti-Alzheimer potential of Tamarindus indica: an in vivo investigation supported by in vitro and in silico approaches' by Abeer H. Elmaidomy et al., RSC Adv., 2022, 12, 11769-11785, https://doi.org/10.1039/D2RA01340A.

Ureteroscopic lithotripsy of ureteric stone using thulium fiber laser in a pregnant patient, case report.

Nephrolithiasis represents a common cause of non-obstetrical abdominal pain during pregnancy with 1 out of 200 pregnancies being affected. 20%-30% of patients require ureteroscopy. Many studies were done on safety of holmium:yttrium-aluminium-garnet (YAG) during pregnancy but none on Thulium Fiber Laser (TFL). To our knowledge, this is the first reported case of pregnant patient with nephrolithiasis that was treated using ureteroscopy and TFL. We present a 28 years old pregnant woman that presented to our hospital with a left distal ureteric stone. Patient underwent URS and lithotripsy using TFL. The procedure was tolerated with no complications.

Metabolic profiling and biological potential of the marine sponge associated Nocardiopsis sp. UR67 along with docking studies.

This work was performed to dig into the phytochemical composition and bioactivities of Nocardiopsis sp. UR67 associated with the marine sponge Callyspongia sp. It was fermented in suspension and immobilised in calcium alginate bead cultures. The ethyl acetate extracts, afforded from the broth in each case named EG-49 and J-48g, respectively, revealed 16 chemical principles mostly belonging to polyketides, macrolides, and peptides. EG-49 and J-48g displayed anti-Candida albicans activity with IC50 values of 8.1 and 8.3 µg/mL, and a substantial cytotoxic effect against lung adenocarcinoma H1650 at IC50 12.6 and 13.7 µg/mL, respectively. However, only EG-49 exhibited a noteworthy anti-trypanosomal activity at 7.5 µg/mL. Molecular docking of the characterised compounds against Trypanosoma brucei trypanothione reductase demonstrated the highest binding models of griseochelin-methyl ester (9) and filipin-II (11), which drew considerable significance of the metabolites derived from Nocardiopsis sp. UR67 developing potential T. brucei trypanothione reductase inhibitors.

Metabolomic profiling and cytotoxic potential of three endophytic fungi of the genera Aspergillus, Penicillium and Fusarium isolated from Nigella sativa seeds assisted with docking studies.

The main aim of our study is to investigate the anticancer potential of our cultivated entophytic fungal strains from Nigella sativa seeds. The strains were identified by sequencing of the partial 18S rRNA gene and the internal transcribed spacer (ITS) region as Aspergillus sp. (SA4), Penicillium sp. (SA5), and Fusarium sp. (SA6). We carried out metabolic profiling for three fungal strains to investigate their metabolites diversity. Profiling of the different extracts revealed their richness in diverse metabolites and consequently fourteen compounds (1-14) were annotated. In addition, the obtained extracts were examined against three cell lines HepG2, MCF-7 and Caco-2 showed activity with IC50 values in the range of 1.95-39.7 µg/mL. Finally, molecular docking study was performed showing questinol as the lowest glide binding score value (-5.925 kcal/mol) among all identified compounds. Our results showed Nigella sativa-associated endophytes as a promising source for further studies to look for anticancer secondary metabolites.

Anti-Alzheimer Potential of a New (+)-Pinitol Glycoside Isolated from Tamarindus indica Pulp: In Vivo and In Silico Evaluations.

Tamarindus indica Linn (tamarind, F. Leguminosae) is one of the most widely consumed edible fruits in the world. Phytochemical investigation of tamarind pulp n-butanol fraction yielded one new (+)-pinitol glycoside compound 1 (25% w/w), and 1D, 2D NMR, and HRESIMS investigation were used to confirm the new compound's structure. (+)-Pinitol glycoside showed anti-Alzheimer potential that was confirmed in prophylactic and treatment groups by decreasing time for the T-maze test; decreased TAO, brain and serum AChE, MDA, tau protein levels, and ß amyloid peptide protein levels; and increasing GPX, SOD levels, and in vivo regression of the neurodegenerative features of Alzheimer's dementia in an aluminum-intoxicated rat model. The reported molecular targets for human Alzheimer's disease were then used in a network pharmacology investigation to examine their complex interactions and identify the key targets in the disease pathogenesis. An in silico-based analysis (molecular docking, binding free energy calculation (ΔGBinding), and molecular dynamics simulation) was performed to identify the potential targets for compound 1. The findings of this study may lead to the development of dietary supplements for the treatment of Alzheimer's disease.