Premarket Evidence and Postmarketing Requirements for Real-Time Oncology Review Indication Approvals.

This cross-sectional study evaluates the use of the US Food and Drug Administration's Real-Time Oncology Review (RTOR) program in confirming the effectiveness of cancer drugs.

Epigenetic Impact of Curcumin and Thymoquinone on Cancer Therapeutics.

Today, one of the most prevalent reasons for death among people is carcinoma. Because it is still on the increase throughout the world, there is a critical need for in- -depth research on the pathogenic mechanisms behind the disease as well as for efficient treatment. In the field of epigenetics, gene expression alterations that are inherited but not DNA sequence changes are investigated. Three key epigenetic changes, histone modifications, DNA methylation and non-coding RNA (ncRNA) expression, are principally responsible for the initiation and progression of different tumors. These changes are interconnected and constitute many epigenetic changes. A form of polyphenolic chemical obtained from plants called curcumin has great bioactivity against several diseases, specifically cancer. A naturally occurring substance called thymoquinone is well-known for its anticancer properties. Thymoquinone affects cancer cells through a variety of methods, according to preclinical studies. We retrieved information from popular databases, including PubMed, Google Scholar, and CNKI, to summarize current advancements in the efficiency of curcumin against cancer and its epigenetic regulation in terms of DNA methylation, histone modifications, and miRNA expression. The present investigation offers thorough insights into the molecular processes, based on epigenetic control, that underlie the clinical use of curcumin and thymoquinone in cancerous cells.

Psyllium and okra mucilage as co-carrier wall materials for fenugreek oil encapsulation and its utilization as fat replacers in pan bread and biscuit production.

This study aimed to investigate the potential use of okra and psyllium mucilage as co-carrier wall materials with whey protein and gum Arabic polymers for encapsulation of fenugreek oil to mask its undesirable flavor and promote their health benefits. Particle size, zeta potential, encapsulation efficiency, morphological properties and fatty acid profiles of crude and encapsulated oils were examined using zeta-sizer, SEM and GC-MS techniques. Crude and encapsulated fenugreek oils were added as functional ingredients during production of pan bread and biscuits. The quality characteristics (baking quality, color and organoleptic properties) of bread and biscuits as well as microbiological properties of bred samples were evaluated. Results showed that the forming microcapsules had sphere particles with the size of 5.05 and 31.64 µm for okra and pysillium mucilage, respectively and had smooth continuous surfaces with no holes or fractures. Fatty acids analysis showed that fenugreek oil is superior functional edible oil, rich in unsaturated fatty acids. The organoleptic properties of products were improved when fat replaced with encapsulated fenugreek oil with okra or psyllium mucilage. Likewise, encapsulated fenugreek oil showed antimicrobial activity in bread samples during storage period. On contrary, Bread and biscuits incorporated with crude fenugreek oil gained the lowest scores for all organoleptic parameters. Regarding these results, encapsulated fenugreek oil presents good fat alternatives in dough formulations with acceptable technological, sensory and antimicrobial properties. However, further investigations still needed regarding the biological activity of encapsulated fenugreek oil and its utilization as a food supplement in other food products.

Prevalence and correlates of generalized anxiety disorder and perceived stress among Sudanese medical students.

BACKGROUND: Generalized Anxiety Disorder (GAD) causes significant disturbance in an individual's well-being and activity. Whereby, interfering with the dynamic progress in life. Also, anxiety is a product of stress and a major predictor of academic performance. This study aimed to assess the prevalence of Generalized Anxiety Disorder (GAD), measure levels of anxiety and perceived stress, evaluate the academic profile, identify lifestyle characteristics, and explore the relationship between these factors. METHODS: In this cross-sectional study, 340 Sudanese medical students filled out online questionnaires, composed of the sociodemographic and lifestyle characteristics, academic profile, Generalized Anxiety Disorder-2 scale (GAD-2), and Perceived Stress Scale-10 (PSS-10). Descriptive and inferential statistics were applied using Statistical Package for Social Science (SPSS) Version 20.0 for data analysis. RESULTS: Of 340 medical students, 3.8% of them were diagnosed with GAD, while 29.1% scored ≥ 3 in GAD-2, indicating a possible diagnosis. The study found that 9.7% of the participants used addictive substances, with 42% of them having high GAD-2 scores. Moreover, high anxiety levels were associated with high-stress scores (p-value = 0.000). Also, high GAD-2 scores were significantly associated with students who spent less than 10,000 SDG (18 USD) weekly, spent more time on entertainment using smart devices (p-value = 0.004), and had an unhealthy diet (p-value = 0.004). Low anxiety levels were associated with better sleep quality (p-value = 0.00), satisfaction with religious practices (p-value = 0.00), and increased leisure/hobby time (p-value = 0.018). High-stress levels were observed in females (p-value = 0.035), those with lower academic performance satisfaction levels, and increased hours of smart device usage for entertainment (p-value = 0.001). Reduced stress levels were associated with being ≥ 23 years old, increased leisure/hobby time (p-value = 0.002), satisfaction with religious practices [F(3, 166.6) = 10.8, p-value = 0.00)], and having a healthy diet (p-value = 0.006). CONCLUSION: The low prevalence of GAD corresponded with previous literature, but 29.1% of medical students had a high probability of having GAD. The study emphasizes on providing accessible mental health services for medical students and interventions addressing modifiable risk factors.

Preoperative Frailty and Malnutrition in Surgical Oncology Patients Predicts Higher Postoperative Adverse Events and Worse Survival: Results of a Blinded, Prospective Trial.

BACKGROUND: Frailty, a multidimensional state leading to reduced physiologic reserve, is associated with worse postoperative outcomes. Despite the availability of various frailty tools, surgeons often make subjective assessments of patients' ability to tolerate surgery. The Risk Analysis Index (RAI) is a validated preoperative frailty assessment tool that has not been studied in cancer patients with plans for curative-intent surgery. METHODS: In this prospective, surgeon-blinded study, patients who had abdominal malignancy with plans for resection underwent preoperative frailty assessment with the RAI and nutrition assessment by measurement of albumin, prealbumin, and C-reactive protein (CRP). Postoperative outcomes and survival were assessed. RESULTS: The study included 220 patients, 158 (72%) of whom were considered frail (RAI ≥21). Frail patients were more likely to be readmitted within 30 and 90 days, (16% vs. 3% [P = 0.006] and 16% vs. 5% [P = 0.025], respectively). Patients with abnormal CRP, prealbumin, and albumin experienced higher rates of unplanned intensive care unit admission (CRP [27% vs. 8%; P < 0.001], albumin [30% vs. 10%; P < 0.001], prealbumin [29% vs. 9%; P < 0.001]) and increased postoperative mortality at 90 and 180 days. Survival was similar for frail and non-frail patients. In the multivariate analysis, frailty remained an independent risk factor for readmission (hazard ratio, 5.58; 95% confidence interval, 1.39-22.15; P = 0.015). In the post hoc analysis using the pre-cancer RAI score, the postoperative outcomes did not differ between the frail and non-frail patients. CONCLUSION: In conjunction with preoperative markers of nutrition, the RAI may be used to identify patients who may benefit from additional preoperative risk stratification and increased postoperative follow-up evaluation.

Synergistic Combination of Letrozole and Berberine in Ascorbic Acid-Stabilized AuNPs: A Promising Solution for Breast Cancer.

Breast cancer is a deadly disease that affects countless women worldwide. The most conventional treatments for breast cancer, such as the administration of anticancer medications such as letrozole (LTZ), pose significant barriers due to the non-selective delivery and low bioavailability of cytotoxic drugs leading to serious adverse effects and multidrug resistance (MDR). Addressing these obstacles requires an innovative approach, and we propose a combined strategy that synergistically incorporates LTZ with berberine (BBR) into stabilised AuNPs coated with ascorbic acid (AA), known as LTZ-BBR@AA-AuNPs. The LTZ-BBR@AA-AuNPs, a novel combined drug delivery system, were carefully designed to maximise the entrapment of both LTZ and BBR. The resulting spherical nanoparticles exhibited remarkable efficiency in trapping these two compounds, with rates of 58% and 54%, respectively. In particular, the average hydrodynamic diameter of these nanoparticles was determined to be 81.23 ± 4.0 nm with a PDI value of only 0.286, indicating excellent uniformity between them. Furthermore, their zeta potential was observed to be -14.5 mV, suggesting high stability even under physiological conditions. The release profiles showed that after being incubated for about 24 h at pH levels ranging from acidic (pH = 5) to basic (pH = 7), the percentage released for both drugs ranged from 56-72%. This sustained and controlled drug release can reduce any negative side effects while improving therapeutic efficacy when administered directly to cancer. MDA-MB-231 cells treated with LTZ-BBR@AA-AuNPs for 48 h exhibited IC50 values of 2.04 ± 0.011 µg/mL, indicating potent cytotoxicity against cells. Furthermore, the nanoparticles demonstrated excellent stability throughout the duration of the treatment.

The Effectiveness of Anti-Interleukin-17A Treatment for Pityriasis Rubra Pilaris: A Systematic Review.

Anti-interleukin-17A (anti-IL-17A) therapy has been increasingly employed as a treatment option for pityriasis rubra pilaris (PRP). In this study, we reviewed all available studies on this topic in the literature to evaluate the efficacy and safety of anti-IL-17A. Our main objective was to assess the current evidence on the efficacy and safety of anti-IL-17A therapy in the management of PRP. We searched for relevant articles on PubMed, MEDLINE, Ovid, Embase, and the Web of Science electronic databases from inception until 2022. Our inclusion criteria were as follows: randomized controlled trials (RCTs), quasi-randomized trials, or prospective observational studies that include PRP patients treated with biological treatments; studies that report clinical outcomes; and studies that compare the treatment modalities, including anti-IL-17, in the English language. A total of 19 articles involving 77 cases were reviewed after applying the inclusion criteria and removing duplicates. We found that type 1 PRP was the most common condition irrespective of gender, and the trunk was the most affected area. The study showed that IL-17 inhibitors had a significant impact on the patients. However, higher-level studies are required to further evaluate the therapeutic and safety effects of the treatment.

Controlling Pharmaceutical Costs in a Student-Run Free Clinic in a Resource-Limited Patient Setting.

Our institution's student-run free clinic has been able to offer medication at no out-of-pocket cost to all patients since it opened in 2004. We have employed two strategies to manage prescription drug costs while simultaneously increasing medication coverage: (1) using Patient Drug Assistance Programs (PDAPs) and (2) developing an institutional-level partnership with pharmaceutical charities for medication subsidization. In this study, we aimed to analyze the financial impact of these measures on the clinic.A query of clinic data over the past 5 years identified 299 active PDAPs, corresponding to 299 fully-subsidized prescriptions. In 2017, there were 35 active PDAPs, increasing to 52 (2018), 62 (2019), and 82 (2020) before a decline to 68 PDAPs in 2021. The company affiliated with the most PDAPs varied annually: GlaxoSmithKline (2017), Lilly (2018, 2019, 2020), and both GlaxoSmithKline and Lilly (2021). The most frequent medications were sitagliptin (2017), insulin (2018, 2019), albuterol (2017, 2018), and dulaglutide (2020, 2021).In addition, data extracted from the private company subsidization program was analyzed for the year 2021. Program membership was $10,000 for institution-wide medication subsidization for all uninsured patients in the hospital system. In total, the clinic was able to acquire 220 medications with a 96% subsidy, corresponding to a direct clinic cost of $2,101.28. Comparatively, the market value of these medications was $52,401.51.Utilization of free drug acquisition programs and partnerships with pharmaceutical charities allowed for an increase in cost-savings and medications provided. Although the process for applying for medication assistance programs is complex, these programs serve as powerful tools for providing medications that may otherwise be unavailable due to cost. Other clinics and healthcare settings with uninsured patients should consider these programs as a means to ease medication cost burden.

Caraway Nanoemulsion Gel: A Potential Antibacterial Treatment against Escherichia coli and Staphylococcus aureus.

Novel antibiotics are needed due to the rise of antibiotic-resistant pathogens. Traditional antibiotics are ineffective due to antibiotic-resistant microorganisms, and finding alternative therapies is expensive. Hence, plant-derived caraway (Carum carvi) essential oils and antibacterial compounds have been selected as alternatives. In this, caraway essential oil as an antibacterial treatment was investigated using a nanoemulsion gel. Using the emulsification technique, a nanoemulsion gel was developed and characterized in terms of particle size, polydispersity index, pH, and viscosity. The results showed that the nanoemulsion had a mean particle size of 137 nm and an encapsulation efficiency of 92%. Afterward, the nanoemulsion gel was incorporated into the carbopol gel and was found to be transparent and uniform. The gel had in vitro cell viability and antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The gel safely delivered a transdermal drug with a cell survival rate of over 90%. With a minimal inhibitor concentration (MIC) of 0.78 mg/mL and 0.78 mg/mL, respectively, the gel demonstrated substantial inhibition for E. coli and S. aureus. Lastly, the study demonstrated that caraway essential oil nanoemulsion gels can be efficient in treating E. coli and S. aureus, laying the groundwork for the use of caraway essential oil as an alternative to synthetic antibiotics in the treatment of bacterial infections.

Antioxidant, Antibacterial, and Anticancer Activity of Ultrasonic Nanoemulsion of Cinnamomum Cassia L. Essential Oil.

Cinnamomum cassia (C. assia) has long been used in traditional holistic medicine for its medicinal properties. It is used as an antioxidant, antibacterial, anti-inflammatory and anticancer agent. Cinnamon, in particular, the essential oil of C. cassia, has significant biological properties. Despite this, the volatility, stability, and insolubility of C. cassia essential oil (CEO) remain the main disadvantages that limit its application, ultimately affecting its pharmacological efficacy. To find a solution to this problem, we developed the CEO nanoemulsion (CEO-NE). For lipophilic compounds, insoluble nanoemulsion-based formulations are a popular delivery strategy. In this research work, a highly stable dosage form named CEO-NE was successfully developed using polysorbate 80 and water. The findings show that the synthesized CEO has a uniform shape with a PDI of 0.380 and an adequate particle size of 221.8 nm. The antioxidant outcomes show excellent results for CEO-NE compared to CEO against DPPH and hydrogen peroxide. The obtained antibacterial activity of CEO-NE was more efficient than that of CEO against Klebsiella pneumonia (MTCC 8911) with 0.025% and 0.05%, respectively. The CEO-NE preparation was tested against an alveolar lung adenocarcinoma cell line (A549) with an IC50 of 50.21 µg/mL for CEO and 18.05 µg/mL for CEO-NE, respectively. These results are encouraging for future translational studies on CEO-NE use in lung cancer therapy due to its excellent antioxidant, antibacterial, and killing kinetic properties.

Anticholinergic effect of resveratrol with vitamin E on scopolamine-induced Alzheimer's disease in rats: Mechanistic approach to prevent inflammation.

The most common form of dementia, Alzheimer's disease (AD), is characterized by gradual declines in cognitive abilities and behavior. It is caused by a combination of factors, including amyloid-ß (Aß) accumulation, acetylcholine (ACh) loss, oxidative stress, and inflammation. Phenolic compounds have a variety of health benefits, including antioxidant activities. Thus, the purpose of this study was to investigate how resveratrol (RES) alone and in combination with vitamin E affected rats with AD using scopolamine (SCO). Animals are categorized into groups; (i) control, (ii) SCO (1 mg/kg i.p.), (iii) SCO + donepezil, (iv) SCO + RES (50 mg/kg, p.o.), (v) SCO + RES (75 mg/kg, p.o.), (vi) SCO + RES (50 mg/kg + vitamin E 1 mg/kg, p.o.) for 17 days. In rats, studied behavioural (NOR and EPM) and biochemical characteristics. In addition, brain histopathology was examined to investigate any damage to the hippocampus and neuroprotection. SCO-induced changes in acetylcholinesterase, protein carbonyl, and TNF-α improved after resveratrol treatment. RES increased antioxidant levels, decreased SCO-induced lipid peroxidation, and reversed SCO-mediated changes compared with the drug donepezil. The results indicated that RES and vitamin E had nootropic action in the NOR and EPM tests, measured by the recognition index and the inflection ratio. This study supports the efficacy of RES as a preventive and treatment agent for AD. Vitamin E showed a synergistic effect on RES, which helps in managing cognitive impairment AD.

Nematicidal activity of sweet annie and garden cress nano-formulations and their impact on the vegetative growth and fruit quality of tomato plants.

Root-knot nematode is one of the major problems that face the agricultural production of several vegetable crops. Chemical nematicides have been banned because of their healthy and environmental undesirable attributes. So, this study aimed to evaluate the potential use of sweet annie (Artimisia annua) and garden cress (Lepidium sativum) as green routes for the development of effective and eco-friendly alternative nematicides. Nematicidal activity of sweet annie and garden cress aqueous extracts (500 g/L) in the original and nano-forms were evaluated against Meloidogyne incognita in tomato planted in infected soil under greenhouse conditions. Nineteen phenolic compounds were identified in A. annua extract, which was dominated by chlorogenic acid (5059 µg/100 mL), while 11 compounds were identified in L. sativum extract, that dominated by p-hydroxybenzoic acid (3206 µg/100 mL). Nano-particles were characterized with smooth surface, spherical shape and small size (50-100 nm). Under laboratory, the nano-formulations showed mortality percentage of M. incognita J2 greater than the original extract from. Vegetative growth parameters of tomato plants treated with A. annua and L. sativum extracts significantly improved compared to the control plants. Also, biochemical analysis revealed that the extracts were able to induce tomato plants towards the accumulation of phenolic compounds and increasing the activity of defensive enzymes (protease, polyphenol oxidase and chitinase) resulting in systemic resistance. Regarding tomato fruits yield and quality, the studied treatments significantly improved the yield and physicochemical parameters of tomato fruits in terms of fruit weight, diameter, TSS, pH, lycopene content and color attributes gaining higher sensorial acceptance by the panelist. Generally, both extracts represent promising nematicide alternatives and have potential use in crop management. The nano-form of A. annua extract outperformed the nematicidal activity of other studied treatments.

Quercetin Attenuates Nitroglycerin-Induced Migraine Headaches by Inhibiting Oxidative Stress and Inflammatory Mediators.

This study aimed to investigate the antimigraine potential of quercetin in migraine pain induced by nitroglycerin (NTG), 10 mg/kg, intraperitoneal injection in rats. Quercetin was administered orally for 1 week, and behavioral parameters associated with pain were assessed 30 min after NTG injection. At the end of the study, the rats were killed so that immunohistochemical examination of their brains could be performed. The time and frequency of rearing and sniffing in the category of exploratory behavior, walking in the category of locomotor behavior, and total time spent in the light chamber were reduced in the disease control group compared with the normal group during the assessment of behavioral parameters. Pathologic migraine criteria, such as increased levels of calcitonin gene-related peptide and increased release of c-fos cells, were more prominent in the caudal nucleus triceminalis of the NTG control group. In the treatment groups, behavioral and pathological measures were less severe after pretreatment with quercetin at doses of 250 and 500 mg/kg. Therefore, it was concluded that quercetin improved the pain behavior of migraine patients in the NTG-induced migraine rat model. Quercetin is thought to have antimigraine effects due to its antioxidant and anti-inflammatory potential. Quercetin may therefore be a novel agent that can treat or prevent migraine pain and associated avoidance behaviors.

Herbal Fennel Essential Oil Nanogel: Formulation, Characterization and Antibacterial Activity against Staphylococcus aureus.

Antimicrobial resistance (AMR) is one of the greatest threats to humanity in the world. Antibiotic-resistant bacteria spread easily in communities and hospitals. Staphylococcus aureus (S. aureus) is a serious human infectious agent with threatening broad-spectrum resistance to many commonly used antibiotics. To prevent the spread of pathogenic microorganisms, alternative strategies based on nature have been developed. Essential oils (EOs) are derived from numerous plant parts and have been described as antibacterial agents against S. aureus. Fennel essential oils were selected as antibacterial agents encapsulated in nanoparticles of polylactic acid and glycolic acid (PLGA). The optimum size of the formulation after loading with the active ingredient was 123.19 ± 6.1595 nm with a zeta potential of 0.051 ± 0.002 (23 ± 1.15 mV). The results of the encapsulation efficiency analysis showed high encapsulation of EOs, i.e., 66.4 ± 3.127. To obtain promising carrier materials for the delivery of fennel EOs, they were incorporated in the form of nanogels. The newly developed fennel oils in PLGANPs nanogels have good drug release and MIC against S. aureus. These results indicate the potential of this novel delivery system for antimicrobial therapy.

Site-Specific Evaluation of Bioactive Coumarin-Loaded Dendrimer G4 Nanoparticles against Methicillin Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a foremost treatment challenge in today's clinical practice. Natural coumarins contain a variety of bioactivities and have the ability to alter resistance in several ways. In developing effective drug delivery methods, the goal is to maximize biocompatibility while minimizing toxicity. With this in mind, this work investigated the site-specific potential of dendrimer G4 poloxamer nanoparticles loaded with bioactive coumarin. The goal of the current work is to deliver a complete evaluation of dendrimer G4 poloxamer nanoparticles against MRSA. Coumarin-loaded dendrimer G4 poloxamer nanoparticles were thoroughly investigated and characterized using various techniques, including particle size, shape, entrapment efficiency, in vitro drug release, hemolysis assay, cytotoxicity, antibacterial activity, and bactericidal kinetics. Studies showed that the newly developed dendrimer G4 poloxamer nanoparticles exhibited significantly lower levels of hemolysis and cytotoxicity. The results showed that the in vitro drug release of coumarin from dendrimer G4 poloxamer nanoparticles was slower compared to coumarin in its free form. This innovative therapeutic delivery technology may enhance the defense of coumarin against MRSA.

Potential Active Constituents from Opophytum forsskalii (Hochst. ex Boiss.) N.E.Br against Experimental Gastric Lesions in Rats.

Opophytum forsskalii (O. forsskalii) is a desert plant that belongs to the Aizoaceae family. Although it is a natural food source for Bedouin tribes in northern Saudi Arabia, there is little information on its active metabolites. Therefore, the secondary metabolites of the hydroalcoholic extract from the leaves of this species were analyzed by liquid chromatography-mass chromatography (LC-MS). LC-MS identified a total of 30 secondary metabolites. These compounds represented two main categories among sixteen classes. Among them, flavonoids represented the largest proportion with eleven metabolites while fatty acids provided seven compounds. In addition, the extract was evaluated for its gastroprotective effect against gastric lesions induced by different models, such as indomethacin, stress, and necrotizing agents (80% ethanol, 0.2 mol/L NaOH, and 25% NaCl), in rats. For each method, group 1 was used as the control group while groups 2 and 3 received the leaf extract at doses of 200 and 400 mg/kg, respectively. The ulcer index (UI) and intraluminal bleeding score (IBS) were measured for each method. In addition, gastric tissue from the ethanol method was used for the analysis of nonprotein sulfhydrates (NP-SH), malondialdehyde (MDA), total protein (TP), and histopathologic evaluation. Pretreatment with O. forsskalii significantly decreased UI (p < 0.01) and IBS (p < 0.01) at 400 mg/kg. Pretreatment with O. forsskalii significantly improved total protein levels (p < 0.01) and NP-SH (p < 0.001) compared to the ethanol ulcer groups. MDA levels increased from 0.5 to 5.8 nmol/g in the normal groups compared to the ethanol groups and decreased to 2.34 nmol/g in the O. forsskalii pretreatment. In addition to the gastroprotective markers, histopathological examination of gastric tissue confirmed the gastroprotective potential of O. forsskalii extract against ethanol.

Bi-allelic loss-of-function variants in TMEM147 cause moderate to profound intellectual disability with facial dysmorphism and pseudo-Pelger-Huët anomaly.

The transmembrane protein TMEM147 has a dual function: first at the nuclear envelope, where it anchors lamin B receptor (LBR) to the inner membrane, and second at the endoplasmic reticulum (ER), where it facilitates the translation of nascent polypeptides within the ribosome-bound TMCO1 translocon complex. Through international data sharing, we identified 23 individuals from 15 unrelated families with bi-allelic TMEM147 loss-of-function variants, including splice-site, nonsense, frameshift, and missense variants. These affected children displayed congruent clinical features including coarse facies, developmental delay, intellectual disability, and behavioral problems. In silico structural analyses predicted disruptive consequences of the identified amino acid substitutions on translocon complex assembly and/or function, and in vitro analyses documented accelerated protein degradation via the autophagy-lysosomal-mediated pathway. Furthermore, TMEM147-deficient cells showed CKAP4 (CLIMP-63) and RTN4 (NOGO) upregulation with a concomitant reorientation of the ER, which was also witnessed in primary fibroblast cell culture. LBR mislocalization and nuclear segmentation was observed in primary fibroblast cells. Abnormal nuclear segmentation and chromatin compaction were also observed in approximately 20% of neutrophils, indicating the presence of a pseudo-Pelger-Huët anomaly. Finally, co-expression analysis revealed significant correlation with neurodevelopmental genes in the brain, further supporting a role of TMEM147 in neurodevelopment. Our findings provide clinical, genetic, and functional evidence that bi-allelic loss-of-function variants in TMEM147 cause syndromic intellectual disability due to ER-translocon and nuclear organization dysfunction.

Phytochemical Screening, In Vitro and In Silico Studies of Volatile Compounds from Petroselinum crispum (Mill) Leaves Grown in Saudi Arabia.

The herbal plant Petroselinum crispum (P. crispum) (Mill) is commonly available around the world. In this study, the leaves of the herbal plant P. crispum were collected from the central region of Al-Kharj, Saudi Arabia, to explore their in vitro pharmacological activity. Essential oil from the leaves of P. crispum was isolated using the hydrodistillation method. The composition of P. crispum essential oil (PCEO) was determined using Gas chromatography-mass spectrometry (GC-MS). A total of 67 components were identified, representing approximately 96.02% of the total volatile composition. Myristicin was identified as the principal constituent (41.45%). The in vitro biological activity was assessed to evaluate the antioxidant, antimicrobial, and anti-inflammatory potential of PCEO. PCEO showed the highest antimicrobial activity against Candida albicans and Staphylococcus aureus among all the evaluated microbial species. In vitro anti-inflammatory evaluation using albumin and trypsin assays showed the excellent anti-inflammatory potential of PCEO compared to the standard drugs. An in silico study of the primary PCEO compound was conducted using online tools such as PASS, Swiss ADME, and Molecular docking. In silico PASS prediction results supported our in vitro findings. Swiss ADME revealed the drug likeness and safety properties of the major metabolites present in PCEO. Molecular docking results were obtained by studying the interaction of Myristicin with an antifungal (PDB: 1IYL and 3LD6), antibacterial (PDB: 1AJ6 and 1JIJ), antioxidant (PDB: 3NM8 and 1HD2), and anti-inflammatory (3N8Y and 3LN1) receptors supported the in vitro results. Therefore, PCEO or Myristicin might be valuable for developing anti-inflammatory and antimicrobial drugs.

Determination of Chemical Composition, In Vitro and In Silico Evaluation of Essential Oil from Leaves of Apium graveolens Grown in Saudi Arabia.

The aim of this study was to explore the composition and evaluate the in silico and in vitro antioxidants and antimicrobial and anti-inflammatory effects of Apium graveolens var. dulce leaves essential oil (AGO) collected from Al-Kharj (Saudi Arabia). AGO was isolated using the hydro-distillation method, and its composition was studied using gas-chromatography-mass Spectrometry (GC-MS), antimicrobial activities using well diffusion assay, and antioxidant and anti-inflammatory activities using spectrophotometric methods. The pharmacological activities of their major compounds were predicted using PASS (prediction of activity spectra for substances) and drug-likening properties by ADME (absorption, distribution, metabolism, and excretion) through web-based online tools. Isocnidilide (40.1%) was identified as the major constituent of AGO along with ß-Selinene, Senkyunolide A, Phytyl acetate, and 3-Butylphthalide. AGO exhibited a superior antibacterial activity, and the strongest activity was detected against Gram-positive bacteria and Candida albicans. Additionally, it exhibited a weaker antioxidant potential and stronger anti-inflammatory effects. PASS prediction supported the pharmacological finding, whereas ADMET revealed the safety of AGO. The molecular docking of isocnidilide was carried out for antibacterial (DNA gyrase), antioxidant (tyrosinase), and anti-inflammatory (cyclooxygenase-2) activities. The docking simulation results were involved hydrophilic interactions and demonstrated high binding affinity of isocnidilide for anti-inflammatory protein (cycloxygenase-2). The presence of isocnidilide makes AGO a potential anti-inflammatory and antimicrobial agent. AGO, and its major metabolite isocnidilide, may be a suitable candidate for the future drug development.