Thymoquinone (Tq) and gallic acid (GA) are known for counter-tumorigenic characteristics. GA inhibits cancer cell proliferation by interfering with many apoptotic signaling pathways, producing more reactive oxygen species (ROS), focusing on the cell cycle, and suppressing the expression of oncogenes and matrix metalloproteinases (MMPs). In this study, thymoquinone (after reducing to thymohydroquinone) and gallic acid are esterified to form thymohydroquinyl gallate (a prodrug). Thymohydroquinyl gallate (THQG) possesses enhanced antineoplastic efficacy and targeted delivery potential. The chemical and spectroscopic analysis confirms ester synthesis. Gold nanoparticles (AuNPs) are employed as nanocarriers due to their physicochemical and optical characteristics, biocompatibility, and low toxicity. As an efficient drug transporter, gold nanoparticles (AuNPs) shield conjugated drugs from enzymatic digestion. The prodrug acts as a reducing agent for Au metal atoms and is loaded onto it after reduction. The nano drug is radiolabeled with ^99mTc and ¹³¹I to monitor the drug biodistribution in animals using a gamma camera and single-photon emission computerized tomography (SPECT). ¹³¹I is an antineoplastic that helps enhance the drug's efficiency. Chromatographic results reveal promising radiolabeling percentages. In vitro, drug release shows sustained release at pH⁓5.8. In vitro 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) cytotoxicity assay reveals drug potency on CAL 27 and MCF 7 cell lines.

Epilepsy surgery is a well-established treatment for drug-resistant epilepsy, with awake craniotomy being used in certain cases to remove epileptogenic foci while preserving crucial brain functions. We are presenting the first reported case from Pakistan of a 19-year-old woman who underwent awake epilepsy surgery to treat cortical dysplasia. She had a history of generalized tonic-clonic seizures since her childhood and was referred to our clinic due to an increase in seizure frequency. EEG and MRI identified the epileptogenic focus in the right parieto-temporal region. The patient underwent a neuro-navigation guided awake craniotomy and an excision of the epileptogenic focus in the right parieto-temporal region. The procedure was carried out using a scalp block and dexmedetomidine for conscious sedation, enabling the patient to remain awake throughout the surgery. Intraoperative mapping and electrocorticography were used for complex multidisciplinary care. Post-resection corticography showed no spikes along the resected margins. The patient was discharged without any complications and remained free of symptoms a year after the surgery. Awake epilepsy surgery is a viable option for removing epileptogenic foci while preserving vital cognitive functions. However, it is seldom used in low- and middle-income countries such as Pakistan. The successful outcome of this case underscores the need for greater awareness and availability of epilepsy surgery in resource-limited settings. Cost-effective measures, such as using small subdural strips for intraoperative localization, can be implemented.

Congenital insensitivity to pain with anhidrosis is a rare autosomal recessive disorder presenting with loss of pain sensation, thermal sensation defects, and self-mutilating behavior. In the present study, we recruited two consanguineous pedigree showing pain insensitivity symptoms from Pakistan for clinical and molecular investigations. In family A, one female patient displayed classical CIPA symptoms along with microcephaly and severe intellectual disability. During course of the disease, her right foot was amputated and had remarkable dental degeneration and teeth shedding. In family B, one boy presented with classical symptoms of congenital insensitivity to pain with anhidrosis. Blood was collected from both families for molecular studies. Sequencing with the Ilumina Trusight One Sequencing Panel covering 4813 OMIM genes revealed a known homozygous mutation c.2084C>T; p.P695L of NTRK1 in family A and a novel truncated mutation c.2025C>G; p.Y681X in family B. Protein modeling analysis of both mutations (p.P695L and p.Y681X) predicted loss of the rigidity in tyrosine kinase domain of NTRK1 that led to conformational changes as well as deleterious effect on protein function. The known mutation was reported more than a decade ago in a family from Northern Israel and other non-sense mutation is newly identified. It is interested that most of NTRK1 mutations are associated with this domain. This is first ever report of NTRK1 variants in congenital insensitivity to pain with anhidrosis patients from Pakistan.
Pain Insensitivity, Congenital