Cuproptosis, a recently identified form of regulated cell death triggered by excess intracellular copper, has emerged as a promising cytotoxic strategy for cancer therapy. However, the therapeutic efficacy of copper ionophores such as elesclomol (ES) is often hindered by cellular copper homeostasis mechanisms that limit copper influx and cuproptosis induction. To address this challenge, we developed a nanoagent utilizing outer membrane vesicle (OMV) derived from Akkermansia muciniphila (Akk) for co-delivery of antioxidant 1 copper chaperone (Atox1)-targeting siRNA and ES (siAtox1/ES@OMV) to tumors. In vitro, we demonstrated that Atox1 knockdown via siRNA significantly disrupted copper export mechanisms, resulting in elevated intracellular copper levels. Simultaneously, ES facilitated efficient copper influx and mitochondrial transport, leading to Fe-S cluster depletion, increased proteotoxic stress, and robust cuproptosis. In vivo, siAtox1/ES@OMV achieved targeted tumor delivery and induced pronounced cuproptosis. Furthermore, leveraging the immunomodulatory properties of OMVs, siAtox1/ES@OMV promoted T-cell infiltration and the activation of tumor-reactive cytotoxic T cells, enhancing tumor immune responses. The combination of siAtox1/ES-induced cuproptosis and immunogenic cell death synergistically suppressed tumor growth in both subcutaneous breast cancer and orthotopic rectal cancer mouse models. This study highlights the potential of integrating copper homeostasis disruption with a copper ionophore using an immunomodulatory OMV-based vector, offering a promising combinatorial strategy for cancer therapy.

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.

A retrospective study was performed to report the case occurrence of cystic echinococcosis (CE) in three hospitals of north-eastern region in Punjab Province, Pakistan. We reviewed retrospectively the clinical records of patients in 4 hospitals which were diagnosed with CE during 2012–2017. A total of 198 cases, 82 (41.4%) male and 116 (58.6%) females were detected as CE. The most Highest incidence was revealed in.... 21–30 years-old group (24.2%) followed by 41–50 (22.7%), 31–40 (16.2%), 11–20 (13.6%), 51–60 (8.1%), below 10 (5.5%), over 71 (5.1%) and 61–70 year-old group (4.5%). CE was detected in various organs of infected individuals. However, most of CE cases were detected in the liver (47.4%) and lung (18.6%). The present study indicated that CE is more or less prevalent in surveyed areas and one of the most important public health problems in Punjab Province, Pakistan.
Echinococcosis ; Epidemiology ; Female ; Humans ; Incidence ; Liver ; Lung ; Male ; Pakistan ; Public Health ; Retrospective Studies

Objective To predict immunogenic promiscuous T cell epitopes from the polyprotein of the Zika virus using a range of bioinformatics tools. To date, no epitope data are available for the Zika virus in the IEDB database. Methods We retrieved nearly 54 full length polyprotein sequences of the Zika virus from the NCBI database belonging to different outbreaks. A consensus sequence was then used to predict the promiscuous T cell epitopes that bind MHC 1 and MHC II alleles using PorPred1 and ProPred immunoinformatic algorithms respectively. The antigenicity predicted score was also calculated for each predicted epitope using the VaxiJen 2.0 tool. Results By using ProPred1, 23 antigenic epitopes for HLA class I and 48 antigenic epitopes for HLA class II were predicted from the consensus polyprotein sequence of Zika virus. The greatest number of MHC class I binding epitopes were projected within the NS5 (21%), followed by Envelope (17%). For MHC class II, greatest number of predicted epitopes were in NS5 (19%) followed by the Envelope, NS1 and NS2 (17% each). A variety of epitopes with good binding affinity, promiscuity and antigenicity were predicted for both the HLA classes. Conclusion The predicted conserved promiscuous T-cell epitopes examined in this study were reported for the first time and will contribute to the imminent design of Zika virus vaccine candidates, which will be able to induce a broad range of immune responses in a heterogeneous HLA population. However, our results can be verified and employed in future efficacious vaccine formulations only after successful experimental studies.