Synthesis, enzyme inhibition assay, and molecular modeling study of novel pyrazolines linked to 4-methylsulfonylphenyl scaffold: antitumor activity and cell cycle analysis.

Antitumor activity using 59 cancer cell lines and enzyme inhibitory activity of a newly synthesized pyrazoline-linked 4-methylsulfonylphenyl scaffold (compounds 18a-q) were measured and compared with those of standard drugs. Pyrazolines 18b, 18c, 18f, 18g, 18h, and 18n possessed significant antitumor activity, with a positive cytotoxic effect (PCE) of 22/59, 21/59, 21/59, 48/59, 51/59, and 20/59, respectively. The cancer cell lines HL60, MCF-7, and MDA-MB-231 were used to measure the IC50 values of derivatives 18c, 18g, and 18hvia the MTT assay method, and the results were compared with those of reference drugs. Derivatives 18g and 18h showed potent and broad-spectrum antitumor activities against HL60 (IC50 of 10.43, 8.99 µM, respectively), MCF-7 (IC50 of 11.7 and 12.4 µM, respectively), and MDA-MB-231 (IC50 of 4.07 and 7.18 µM, respectively). Compound 18c exhibited strong antitumor activity against HL60 and MDA-MB-231 cell lines with IC50 values of 8.43 and 12.54 µM, respectively, and moderate antitumor activity against MCF-7 cell lines with an IC50 value of 16.20 µM. Compounds 18c, 18g, and 18h remarkably inhibited VEGFR2 kinase (IC50 = 0.218, 0.168, and 0.135 µM, respectively) compared with the reference drug sorafenib (IC50 = 0.041 µM). Compounds 18g and 18h effectively inhibited HER2 kinase (IC50 = 0.496 and 0.253 µM, respectively) compared with erlotinib (IC50 = 0.085 µM). Compound 18h inhibited EGFR kinase (IC50 = 0.574 µM) with a potency comparable with that of the reference drug erlotinib (IC50 = 0.105 µM). Pyrazolines 18c, 18f, and 18h arrested the S/G2 phase of the cell cycle in HL-60 cells. In addition, derivatives 18c, 18f, and 18h revealed lower Bcl-2 protein expression anti-apoptotic levels and higher Bax, caspase-3, and caspase-9 expression levels. Molecular docking studies of derivative 18h into the binding sites of EGFR, HER2, and VEGFR2 kinases explored the interaction mode of these pyrazoline derivatives and their structural requirements for antitumor activity.

Quercetin and Kaempferol as Multi-Targeting Antidiabetic Agents against Mouse Model of Chemically Induced Type 2 Diabetes.

Diabetes, a multifactorial metabolic disorder, demands the discovery of multi-targeting drugs with minimal side effects. This study investigated the multi-targeting antidiabetic potential of quercetin and kaempferol. The druggability and binding affinities of both compounds towards multiple antidiabetic targets were explored using pharmacokinetic and docking software (AutoDock Vina 1.1.2). Our findings showed that quercetin and kaempferol obey Lipinski's rule of five and exhibit desirable ADMET (absorption, distribution, metabolism excretion, and toxicity) profiles. Both compounds showed higher binding affinities towards C-reactive protein (CRP), interleukin-1 (IL-1), dipeptidyl peptidase-4 (DPP-IV), peroxisome proliferator-activated receptor gamma (PPARG), protein tyrosine phosphatase (PTP), and sodium-glucose co-transporter-1 (SGLT-1) compared to metformin (the positive control). Both quercetin and kaempferol inhibited α-amylase activity (in vitro) up to 20.30 ± 0.49 and 37.43 ± 0.42%, respectively. Their oral supplementation significantly reduced blood glucose levels (p < 0.001), improved lipid profile (p < 0.001), and enhanced total antioxidant status (p < 0.01) in streptozotocin-nicotinamide (STZ-NA)-induced diabetic mice. Additionally, both compounds significantly inhibited the proliferation of Huh-7 and HepG2 (cancer cells) (p < 0.0001) with no effect on the viability of Vero cell line (non-cancer). In conclusion, quercetin and kaempferol demonstrated higher binding affinities towards multiple targets than metformin. In vitro and in vivo antidiabetic potential along with the anticancer activities of both compounds suggest promise for further development in diabetes management. The combination of both drugs did not show a synergistic effect, possibly due to their same target on the receptors.

Postoperative Pain Following Transoral Thyroidectomy via Vestibular Approach and Cervical Thyroidectomy: A Systematic Review and Meta-Analysis.

Transoral endoscopic thyroidectomy via the vestibular approach (TOETVA) represents a minimally invasive alternative to traditional open thyroidectomy (OT). The objective of this systematic review and meta-analysis was to comprehensively analyze and compare postoperative pain outcomes between conventional open thyroidectomy (COT) and TOETVA. We conducted a systematic search across multiple databases, including PubMed, Medline, Elton B. Stephens Company (EBSCO), and Google Scholar, to identify cohorts and randomized trials comparing postoperative pain outcomes between patients undergoing transoral endoscopic thyroidectomy via the vestibular approach (TOETVA) and those undergoing conventional thyroidectomy. The search period spanned from the earliest available article up to January 15, 2022. Keywords such as "scarless thyroidectomy," "endoscopic transoral via vestibular thyroidectomy," "conventional thyroidectomy," "transcervical thyroidectomy," "postoperative pain," and "visual analog pain score" were utilized to retrieve relevant studies. A total of 1,291 patients from 11 studies were included in our analysis, with 10 studies originating from Asia and one from Europe. Among these studies, seven were prospective, while four were retrospective. The primary outcome measure was postoperative pain. Various statistical tests were also performed for data analysis, including the Chi-square and random effects model. The Newcastle Ottawa Scale was used to assess the quality of studies. There was no significant statistical difference observed between the endoscopic transoral vestibular route and the conventional cervical approach in terms of visual analog scale (VAS) score, with an odds ratio of -0.37 and a 95% confidence interval ranging from -0.9 to 0.17. The overall effect had a P-value of 0.18. However, substantial heterogeneity was noted, with an I2 value for heterogeneity of 98% and a P-value for heterogeneity of less than 0.001. The Chi-square value was calculated as 364.02, and the main difference was 9. In comparison, TOETVA exhibited lower pain levels on the first day post-operation compared to conventional thyroidectomy, with an odds ratio of -1.36 and a 95% confidence interval ranging from -2.65 to -0.06. Transoral endoscopic thyroidectomy via the vestibular approach demonstrated superior outcomes compared to conventional thyroidectomy in terms of postoperative pain management on the first day following surgery. However, when considering overall pain management throughout the recovery period, no significant difference was observed between the two approaches. More extensive studies evaluating pain levels on the day of surgery and controlling for analgesic interventions are warranted.

Beyond the Pump: A Narrative Study Exploring Heart Memory.

The field of organ transplantation, particularly heart transplantation, has brought to light interesting phenomena challenging traditional understandings of memory, identity, and consciousness. Studies indicate that heart transplant recipients may exhibit preferences, emotions, and memories resembling those of the donors, suggesting a form of memory storage within the transplanted organ. Mechanisms proposed for this memory transfer include cellular memory, epigenetic modifications, and energetic interactions. Moreover, the heart's intricate neural network, often referred to as the "heart brain," communicates bidirectionally with the brain and other organs, supporting the concept of heart-brain connection and its role in memory and personality. Additionally, observations from hemispherectomy procedures highlight the brain's remarkable plasticity and functional preservation beyond expectations, further underscoring the complex interplay between the brain, body, and identity. However, ethical and philosophical questions regarding the implications of these findings, including the definition of death and the nature of personal identity, remain unresolved. Further interdisciplinary research is needed to unravel the intricacies of memory transfer, neuroplasticity, and organ integration, offering insights into both organ transplantation and broader aspects of neuroscience and human identity. Understanding these complexities holds promise for enhancing patient care in organ transplantation and deepens our understanding of fundamental aspects of human experience and existence.

Integrating digital smile design into restorative Dentistry: A narrative review of the applications and benefits.

The primary goal of esthetic treatment is to ensure patient satisfaction and meet their expectations of improving their facial esthetics and smile. However, some patients may have doubts regarding the irreversible nature of the treatment. In such cases, the Digital Smile Designing (DSD) technique can be employed to educate and motivate patients. DSD is a technical tool that allows digital designing and modification of a patient's smile, enabling them to visualize the potential outcomes before the actual treatment begins. This technique facilitates visual communication and patient involvement in the smile design process, leading to predictable treatment results and higher acceptance rates. This article provides an overview of DSD in esthetic dental practice and discusses its applications, advantages, limitations, and future possibilities.

Surgical Interventions for the Management of Obesity-Related Joint Pain: A Narrative Review.

Obesity-related joint pain is a common and debilitating condition that significantly impacts the quality of life, primarily due to the excess weight straining the joints. This results in inflammation and degeneration, which can cause pain, stiffness, and difficulty moving. We aimed to comprehensively review the literature discussing surgical interventions for obesity-related joint pain. We searched across databases (PubMed, Scopus, and Cochrane Library) to identify studies published between 2000 and 2023 that assessed surgical interventions for obesity-related joint pain. This review highlights the complex interplay of mechanical, inflammatory, and metabolic factors contributing to joint pain in obese individuals, highlighting both surgical and non-surgical interventions. Non-surgical interventions include weight loss, exercise, physical therapy, and medications. Surgical interventions include bariatric surgery and joint replacement surgery. Bariatric surgery significantly reduces body weight and improves the quality of life outcomes; however, multiple studies have found no improvement or worsening of joint pain post-surgery. Total joint arthroplasty has demonstrated good improvement in pain and function outcomes based on recent meta-analyses, although risks of complications are higher in obese patients. The treatment choice for obesity-related joint pain depends on the individual patient's circumstances. Non-surgical interventions are usually the first line of treatment. However, if these interventions are not effective, surgical interventions may be an option.

Müller muscle-Conjunctival Resection (MMCR) Surgery: A Comprehensive Literature Review.

PURPOSE: This literature review aims to provide a comprehensive overview of the current understanding, indications, techniques, outcomes, and complications of Müller muscle-conjunctival resection (MMCR) surgery. It also addresses areas of debate with MMCR such as predictability concerning Phenylephrine response as well as the amount of muscle resection required. METHOD: This literature review was compiled based on the available evidence from PubMed from 1975 to August 2023. RESULTS: The success rate of MMCR ranges from 72% to 95%, with high patient satisfaction reported in most studies. The exact range of eyelid elevation after MMCR is variable, with a reported average of 2.1 mm MRD1 elevation. CONCLUSION: MMCR is a well-established surgical technique used to correct upper eyelid ptosis that results from dysfunction or attenuation of the levator aponeurosis. MMCR proved to be a safe and effective procedure with a high patient satisfaction rate and low risk of complications.

Evaluating the effect of NPO status on mucosal coating during double contrast barium esophagrams.

INTRODUCTION: Current guidelines for double contrast barium esophagography studies (BAS) suggest that patients should be nil per os (NPO) prior to completing BAS for optimal esophageal coating, although the time required varies between practices and institutions. It is believed that consumption of food or water disrupts the ability for thick barium contrast to properly coat the esophageal mucosa. Exams that are rescheduled for this reason can lead to delays in care, without substantial evidence that NPO status truly affects esophageal mucosal coating for these exams with current barium mixtures. OBJECTIVE: The study aims to identify the necessity, or lack thereof, of standard NPO protocol in patients undergoing BAS, in effort to prevent unnecessary procedural delay. MATERIALS AND METHODS: This study is an IRB-approved HIPAA-compliant study of 370 consecutive adult patients (115 male/255 female, mean age 55) who underwent BAS at our institution from January to June of 2022. Patients were divided into two groups: < 4 h NPO (n = 334), and ≥ 4 h NPO (n = 36). Four abdominal radiologists blinded to NPO interval independently reviewed a random sample of approximately 92 patients (91-94) and graded esophageal coating on a 4-point-scale with 1 being insufficient coating and 4 being optimal coating. RESULTS: No significant statistical difference in mean esophageal coating score was found between the ≥ 4 h NPO cohort (3.04 ± SD 0.78) and the < 4 h NPO cohort (2.97 ± SD 0.70; P = 0.54). Subset analysis of patients who were NPO for < 2 h (n = 9) also showed no significant difference in mean esophageal coating score (3.11 ± SD 0.6; P = 0.92), compared to the standard ≥ 4 NPO status. CONCLUSION: Non-adherence to standard NPO protocol prior to BAS studies did not result in a significant difference in esophageal coating when compared to traditional preprocedural fasting of 4 or more hours.

Beneath the Surface: Exploring Hidden Threats of Long-Term Corticosteroid Therapy to Bone Density.

Within the field of medical treatments, corticosteroids are potent substances that efficiently reduce inflammation and immunological responses, making them essential for the management of a wide range of medical ailments. However, continued use of these synthetic drugs presents a serious risk: the onset of osteoporosis brought on by corticosteroids. Determining the complex pathways by which corticosteroids cause a general disturbance in bone metabolism, suppress osteoblast function, increase osteoclast activity, and upset the delicate balance of bone remodelling emphasizes the need for all-encompassing management and prevention approaches. In this review, we aim to expose the complexities of corticosteroid-induced bone loss and urge for personalized, proactive measures to improve long-term therapeutic outcomes.

Examining the Quality of Life and Discrimination Impact on Parents of Children With Autism Spectrum Disorder in Aseer Region, Saudi Arabia: A WHO-QOL Survey.

Background Autism spectrum disorder (ASD) is a neurodevelopmental disease marked by social and repetitive or restricted behaviors, as well as communication difficulty. Objectives This survey aimed to assess the quality of life (QoL) of parents with ASDs in the Aseer region of Saudi Arabia using the brief form of the World Health Organization (WHO-QOL) questionnaire. Furthermore, we sought to measure the severity of discrimination experienced by parents of children with ASDs and their impact on QoL. Methodology Using a Google form, a cross-sectional study was carried out online between March and April 2023. The patient records from four different regions of Saudi Arabia were used to recruit study participants. The survey was distributed through well-known social media channels (Instagram, Telegram, Facebook). Results A total of 99 parents were included in this study. The Southern region accounted for the bulk of participants (81.8%, n=81), nearly three-fourths of the children were boys (70.7%), mothers were more common among respondents (65.7%, n=65) than fathers, 66.7% of respondents reported being married, and 78.8% fall into the middle economic class category. The main source of information among the studied population was the Internet (39.4%, n=39), followed by relatives (23.0%, n=23), physicians (8.1%, n=9), and finally books (4%, n=4). The mean scores for the various domains are as follows: physical (58.48 ± 13.84), psychological (62.04 ± 18.08), social relations (61.20 ± 23.24), environment (24.12 ± 14.62), general QoL (72.93 ± 4.30), and general health (73.94 ± 4.63). Nearly half (46.5%) of parents have encountered stigma or discrimination toward their child or family. Individuals who reported experiencing discrimination exhibited significantly lower mean scores in multiple QoL domains than those who did not report discrimination for physical (54.11, ± 14.36vs, 62.26±12.28, p=0.003), psychological (55.80 ± 20.33 vs 67.45 ± 13.94, p=0.002), and social relations (55.43± 24.17 vs 66.20 ± 21.40, p=0.022). Multivariate analysis revealed that discrimination was the only significant predictor of QoL (p < 0.001). Conclusions The QoL of parents having a child with autism is low, moreover, the coincidence of discrimination and stigma significantly lowered QoL.

Synthesis, in silico ADMET prediction analysis, and pharmacological evaluation of sulfonamide derivatives tethered with pyrazole or pyridine as anti-diabetic and anti-Alzheimer's agents.

Based on previous developments of our research programs in trying to find new compounds with multiple biological targets such as antioxidant, anti-diabetic, anti-Alzheimer's, and anti-arthritic agents. In the context, a novel series of sulfonamide derivatives based on the pyrazole or pyridine moieties 3a, b, 7-9, 11-13, 15a, b, and 16 were synthesized from amine compounds with sulfonyl chloride derivatives. The structures of sulfonamide derivatives were elucidated via spectroscopy (1H and 13C NMR). The sulfonamide derivatives were biologically assessed in vitro for their anti-diabetic (α-amylase and α-glucosidase inhibition) and anti-Alzheimer's (acetylcholinesterase inhibition) activities. The biological results revealed that compound 15a is a powerful enzyme inhibitor for α-amylase and α-glucosidase. Also, compound 15b demonstrated inhibitor activity against the acetylcholinesterase enzyme. The structure-activity relationship study of sulfonamide derivatives was accomplished. Furthermore, complementary in silico molecular properties, drug-likeness, ADMET prediction, and surface properties of the two more powerful derivatives 15a and 15b were fulfilled and computed. These studies recommend 15a and 15b as candidates with modifications in their structures before the in vivo assays.

C3-Symmetric ligands in drug design: An overview of the challenges and opportunities ahead.

C3-symmetry is a type of star-shaped molecule consisting of a central core and three symmetrically attached chains. These molecules are used in drug discovery due to their unique three-fold rotational symmetry, which allows for specific binding interactions and improved molecular recognition. In this text, we provide an overview of synthetic approaches with C3-symmetry as a pharmaceutical tool: progress, challenges, and opportunities. C3-symmetric ligands offer both challenges and opportunities in drug design. Their unique symmetry can enhance binding interactions, but careful consideration of rigidity, synthetic complexity, and target compatibility is crucial. Further research and advancements in synthetic methods and modeling tools will likely drive their exploration in drug discovery, leading to the discovery of potent C3-symmetric ligands.

Covalently linked thieno[2,3-b]thiophene-fullerene dimers: synthesis and physical characterization.

Thienothiophene (TT) has received great attention in the fields of electronics and optoelectronics. Here we report a synthesis and characterization of fullerene-donor-fullerene triads linked to thieno[2,3-b]thiophene as a donor. The photophysical and electrochemical properties of the new dumbbells were investigated using UV-vis spectroscopy, fluorescence spectroscopy, cyclic voltammetry, and square wave voltammetry. The results showed that both compounds have higher LUMO energy levels than PC61BM, indicating that they can be used in photovoltaic applications. Furthermore, the powder was structurally and morphologically characterized via X-ray diffraction (XRD) and scanning electron microscopy (SEM). The SEM revealed the morphological characterization of the two derivatives as globular and urchin-like supramolecular assemblies.

Ponatinib: A comprehensive drug profile.

Ponatinib is a prescription medication used to treat a rare form of blood cancer called Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myeloid leukemia (CML) that is resistant to other treatments. It belongs to a class of drugs called tyrosine kinase inhibitors, which work by blocking abnormal proteins that promote the growth of cancer cells. In this chapter, the synthesis methods and physicochemical properties of ponatinib were reviewed, besides the characterization of the ponatinib structure using different techniques such as elemental analysis, IR, UV, (1H and 13C) NMR, MS, and XRD. Furthermore, the compendial method for analysis of ponatinib was not found, while the literature review of a non-compendial method for analysis of ponatinib, such as spectroscopic, chromatographic, and immunoassay methods, was covered. Moreover, pharmacology and biochemistry were surveyed in the pharmacokinetic and pharmacodynamic studies.

Avanafil: A comprehensive drug profile.

Avanafil is an oral medication used to treat erectile dysfunction (ED). As a phosphodiesterase type 5 (PDE5) inhibitor, it functions by inhibiting the PDE5 enzyme, which ultimately results in increased levels of cyclic guanosine monophosphate (cGMP) and improved blood flow to the penis. Approved by the FDA in 2012, avanafil is recognised for its rapid onset of action, short half-life, and favourable side-effects profile. While it has been explored for other potential therapeutic applications, its current approved use is limited to ED and should be used as prescribed by a medical professional. This chapter provides a comprehensive review of avanafil, encompassing its nomenclature, physicochemical properties, methods of preparation, and identification. Various techniques for analysing avanafil, such as electrochemical analysis, spectrophotometric, spectrofluorimetric, and chromatographic techniques, are discussed. The pharmacology of avanafil, including its pharmacokinetics and pharmacodynamics, is also examined.

Regorafenib: A comprehensive drug profile.

Regorafenib is a small molecule tyrosine kinase inhibitor administered orally drug, act by inhibiting the activity of the VEGF receptors. It is used for the treatment of patients with metastatic colorectal cancer (CRC), advanced gastrointestinal stromal tumors, and hepatocellular carcinoma. This comprehensive profile on regorafenib includes an original data as well as data collected from the literature on Profiles of Methods of Drug Synthesis, different Physical Drug Profiles, Drug Analytical methods and Pharmacological profile (ADME). This chapter is divided into five main sections: General Description of the drug, Physical Characteristics, Methods of Preparation, Methods of Analysis, Pharmacology and List of References. These main sections are further divided to many sub-titles to cover most aspect of the drug in the light of the available literature. Among these sub-titles are the formulae, Elemental Analysis, physical characteristics which include constant of ionization, solubility, X-ray powder diffraction pattern, TGA, thermal conduct and spectroscopic and stability. Additionally, analytical techniques including Electrochemical, Spectrophotometric and chromatographic methods, ADME profiles and pharmacological effects were also discussed. Furthermore, methods and schemes are outlined for the preparation of the drug substance.

An advanced case of pediatric ciliary body medulloepithelioma with detailed literature review.

INTRODUCTION AND IMPORTANCE: Medulloepithelioma is the second most common primary intraocular malignant tumor in children but is often diagnosed late, which worsens the prognosis. CASE PRESENTATION: We are reporting a 6-year-old boy presenting with a ciliary body (CB) teratoid malignant medulloepithelioma (TMM), which was missed at the initial presentation. We added our case to the 97 previously reported cases in our literature review that were confirmed by cytological or histopathological examination. DISCUSSION: Medulloepithelioma has a wide age range at presentation with a mean of 5.3 ± 4.1 years, and slight male predominance (M: F ratio of 1.15). Clinically, the main symptoms/ signs are reduced visual acuity, lens changes, or a pupil "mass." Almost all reported medulloepitheliomas were unilateral (98 %). Histopathologically, non-teratoid malignant medulloepithelioma (NTMM) (35.7 %) and TMM (34.5 %) were the commonest. Enucleation was the main treatment modality because of the large tumor size of 72.7 %. A combination of chemotherapy and/or radiotherapy was used in 15.1 % and brachytherapy for small lesions in 14.1 %. Orbital exenteration was needed in 3 cases because of orbital invasion. CONCLUSION: A CB medulloepithelioma tumor can be easily missed, diagnosed late, with less chance for globe salvaging. The malignant types are more common and may result in orbital invasion, requiring even more extensive surgery. Therefore, when facing a child with lens changes, a pupil "mass," or raised intraocular pressure, pediatricians and general ophthalmologists must have an earlier suspicion and be aware of this rare entity to improve outcomes and reduce loss of vision or other disease-related morbidity.

DCR preferences among oculoplastic surgeons: Barriers and facilitators to adoption of endoscopic DCR.

OBJECTIVE: To determine the preference for dacryocystorhinostomy (DCR), patient selection criteria for endoscopic DCR, endoscopic DCR technique, and barriers to adoption of endoscopic DCR. METHOD: Cross-sectional study conducted from May-December 2021. A survey was sent to oculoplastic surgeons. Questions on demographic characteristics, type of clinical practice, technique preferences, barriers and facilitators to adoption of endoscopic DCR were included. RESULTS: 245 participants completed the survey. Most respondents were located at an urban site (84%), were in private practice (66%), and had been in practice for more than 10 years (58.9%). Sixty one percent perform external DCR as the first line procedure for treating primary nasolacrimal duct obstruction. The most common factor influencing the surgeon's decision to perform endoscopic DCR was the patient's request (37%) followed by endonasal exam (32%). The most common barrier for not performing endoscopic DCR was the lack of experience and lack of training during fellowship (42%). The most worrisome complication for most respondents was failure of the procedure (48%), followed by bleeding (30.3%). Eighty one percent believe surgical mentorship and supervision during initial cases would facilitate endoscopic DCR learning. CONCLUSIONS: External Dacryocystorhinostomy is the preferred technique for treating primary acquired nasolacrimal duct obstruction. Learning endoscopic DCR early during fellowship training and high surgical volume to improve the learning curve dramatically impacts the adoption of the procedure.

Orbital abscess with white eye in patients treated with oral antibiotics for orbital cellulitis.

PURPOSE: To report a case series of seven patients with late presentation of orbital/subperiosteal abscess following oral treatment of orbital cellulitis. METHODS: A retrospective case series of all patients presented with orbital abscess following oral treatment of orbital cellulitis from two tertiary-care eye centres in Riyadh, Saudi Arabia, was conducted. Demographic profiles, risk factors, initial clinical presentation, management regimens, and final outcome were analysed. RESULTS: Patients presented mainly with proptosis and limitation of extraocular motility without external ophthalmic inflammatory signs. Most patients needed surgical evacuation despite the appropriate initiation of intravenous antibiotics following presentation to our hospitals. CONCLUSION: Treating orbital cellulitis with oral antibiotics may lead to delayed presentation of orbital abscess without external ophthalmic inflammatory signs.

Biochemical, Toxicological, and in Silico Aspects of Trillium govanianum Wall. ex D.Don (Trilliaceae): A Rich Source of Natural Bioactive Compounds.

Trillium govanianum is a high-value medicinal herb, having multifunctional traditional and culinary uses. The present investigation was carried out to evaluate the phytochemical, biological and toxicological parameters of the T. govanianum Wall. ex D. Don (Family: Trilliaceae) roots collected from Azad Kashmir, Pakistan. Phytochemical profiling was achieved by determining total bioactive contents (total phenolic and flavonoid contents) and UHPLC-MS analysis. For biological evaluation, antioxidant activities (DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum, and metal chelation assays) and enzyme inhibition activities (against AChE, BChE, glucosidase, amylase, and tyrosinase) were performed. Moreover, cytotoxicity was assessed against three human carcinoma cell lines (MDA-MB-231, CaSki, and DU-145). The tested extract was found to contain higher total phenolics (7.56 mg GAE/g dry extract) as compared to flavonoid contents (0.45 mg RE/g dry extract). Likewise, for the antioxidant activity, higher CUPRAC activity was noted with 39.84 mg TE/g dry extract values. In the case of enzyme assays, higher activity was pointed out against the cholinesterase, glucosidase and tyrosinase enzymes. The plant extract displayed significant cytotoxicity against the cell lines examined. Moreover, the in-silico studies highlighted the interaction between the important phytochemicals and tested enzymes. To conclude, the assessed biological activity and the existence of bioactive phytochemicals in the studied plant extract may pave the way for the development of novel pharmaceuticals.