Colorectal cancer (CRC), a major global health concern, necessitates innovative treatments. Chimeric antigen receptor (CAR) T cells have shown promises, yet they grapple with challenges. The spotlight pivots to the rising heroes: CAR natural killer (NK) cells, offering advantages such as higher safety profiles, cost-effectiveness, and efficacy against solid tumors. Nevertheless, the specific mechanisms underlying CAR NK cell trafficking and their interplay within the complex tumor microenvironment require further in-depth exploration. Herein, we provide insights into the design and engineering of CAR NK cells, antigen targets in CRC, and success in overcoming resistance mechanisms with an emphasis on the potential for clinical trials.
Colorectal Neoplasms/immunology* ; Humans ; Killer Cells, Natural/metabolism* ; Receptors, Chimeric Antigen/genetics* ; Immunotherapy, Adoptive/methods* ; Tumor Microenvironment/immunology* ; Animals

Navigation of the main root canal and dealing with a dens invaginatus (DI) is a challenging task in clinical practice. Recently, the guided endodontics technique has become an alternative method for accessing root canals, surgical cavities, and calcified root canals without causing iatrogenic damage to tissue. In this case report, the use of the guided endodontics technique for two maxillary lateral incisors with multiple DIs is described. A 16-year-old female patient was referred with the chief complaint of pain and discoloured upper front teeth. Based on clinical and radiographic findings, a diagnosis of pulp necrosis and chronic periapical abscess associated with double DI (Oehler's type II) was established for the upper left lateral maxillary incisor (tooth #22). Root canal treatment and the sealing of double DI with mineral trioxide aggregate was planned for tooth #22. For tooth #12 (Oehler's type II), preventive sealing of the DI was planned. Minimally invasive access to the double DI and the main root canal of tooth #22, and to the DI of tooth #12, was achieved using the guided endodontics technique. This technique can be a valuable tool because it reduces chair-time and, more importantly, the risk of iatrogenic damage to the tooth structure.
Adolescent ; Dental Pulp Cavity ; Dental Pulp Necrosis ; Diagnosis ; Endodontics ; Female ; Humans ; Incisor ; Methods ; Miners ; Periapical Abscess ; Printing, Three-Dimensional ; Tooth

Cystic Echinococcosis (CE) is one of the most important zoonotic parasitic diseases in human, livestock, and wildlife globally. The prevalence of CE depends upon human behavioral risk factors, the diversity and ecology of animal host interactions and the genetic diversity within Echinococcus species which differ in their zoonotic potential and pathogenicity. It is a neglected, economic and socio-cultural problem in Pakistan. The available data about the incidence of CE is very limited and no extensive study has been reported in Pakistan. The current study was aimed to analyze the hospital reported cases of CE and the associated risk factors related to the incidence of CE. The hospital-based data of CE for the time period of January 2012-December 2017 was collected from Islamabad, Rawalpindi and Peshawar. The data covered demographic characteristics including age, gender, and cyst localization of infected individuals and socioeconomic determinants. The data was analyzed based upon different risk factors along with the different socioeconomic parameters that has an important impact on the distribution of disease. A total of 228 cases were presented in the selected hospitals of different cities during the study period. Out of total 228 patients, 59.21% were males and 40.78% were females (P<0.001). Most infections have been recorded in young adults (>20-30) showing 22.8% of total infected individuals followed by children (0-10) showing 10.5% (n=24), respectively (P<0.001). Liver was the most vulnerable organ (58.77%, n=134) followed by lungs (14.47%, n=33) (P<0.001). The infection was higher among rural communities (84.2%) than urban (12.8%) (P<0.001). Socioeconomic and demographic factors had an important impact on the intensity of disease (P<0.001). The occurrence of cases in children and young adults was an important finding as it indicated an active transmission of the parasite in Pakistan along with the poverty index. Emergence of echinococcosis in Pakistan showed that emerging health issues in Pakistan could bring the disease to limelight for future research. This finding, together with the fact that 1 hospital reported 214 cases over 6 years 325 underlines the need for a program for prevention/control of this disease in Pakistan. The timely measure needs to be taken to hamper the disease development and establishment. In order to control the disease, complete surveillance should be done which in turn weighs down the disease progress.

Impalement injuries, is a severe form of trauma, which are not common in civilian life. These injuries rarely occurs in major accidents. Abdomen, chest, limbs and perineum are often involved due to their large surface area. Thoracic impalement injury is usually a fatal injury, due to location of major vessels and heart in the thoracic cavity. These injuries are horrifying to site, but the patients who are lucky enough to make it to hospital, usually survive. Chances of survival are larger in right sided impalement injuries while central injuries are always died at the scene. Our patient, 25 years old male, was brought to the emergency room (ER) with large impaled metallic bar (about 2.5 feet long) in situ, in right sided chest. The patient was immediately shifted to operation room (OR) and was operated, his recovery was uneventful without any sequelae. Such patients should be treated and resuscitated according to advanced trauma life support (ATLS) protocols and operated without any delay for further investigations. Such operations are carried out by the most experienced surgeon team available. The impaled objects should not be processed if not necessary to avoid major hemorrhage and damage to vital structures, until the patient is in operation room. Large size and unusual position of impaled objects, makes the job difficult for surgeons/anesthetists. Although horrifying at scene, patients with thoracic impalement injuries are mostly young and healthy, and those who survive the pre-hospital phase are potentially manageable with proper resuscitation. Usually these patients make recovery without any further complications.
Accidents, Traffic ; Adult ; Advanced Trauma Life Support Care ; Foreign Bodies ; surgery ; Humans ; Male ; Metals ; Resuscitation ; Survivors ; Thoracic Injuries ; surgery ; Thoracic Surgical Procedures ; methods ; Thorax ; Treatment Outcome ; Wounds, Penetrating ; surgery

The National Cancer Institute had projected breast cancer (BC) as one of the topmost prevalent malignancies around the globe. In many cases, BC becomes resistant to chemotherapy, radiation and hormonal therapies. Traditional BC therapies are associated with adverse side effects, drug resistance and recurrence. Extensive research work has shown that these dietary phytochemicals (DPs) may exert therapeutic effects by regulating the miRNA expression. A large number of DPs have been researched as miRNA regulatory agents against BC and some other DPs have not yet been tested against BC. We have discussed the effects of curcumin, diallyl disulphide, 3,3′ diindolylmethane, ellagic acid, genistein, indole-3-carbinol, quercetin, resveratrol, and sulforaphane on regulation of expression of BC miRNAs in a wide range of in vitro and in vivo models. We have also shown some of the possible DPs (Oleanolic acid, capsaicin, benzyl isothiocyanate, epigallocatechin gallate, phenethyl isothiocyanate and ursolic acid) that have shown miRNA regulatory activities and have not yet been tested against BC miRNAs. Finally, current limitations, challenges, future perspectives of DPs and BC research are also critically discussed.

Cancer is a frightful disease and represents one of the biggest health-care issues for the human race and demands a proactive strategy for cure.Plants are reservoirs for novel chemical entities and provide a promising line for research on cancer.Hitherto,being effective,chemotherapy is accompanied by certain unbearable side effects.Nevertheless,plants and plant derived products is a revolutionizing field as these are Simple,safer,ecofriendly,low-cost,fast,and less toxic as compared with conventional treatment methods.Phytochemicals are selective in their functions and acts specifically on tumor cells without affecting normal cells.Carcinogenesis is complex phenomena that involves many signaling cascades.Phytochemicals are considered suitable candidates for anticancer drug development due to their pleiotropic actions on target events with multiple manners.The research is in progress for developing potential candidates (those can block or slow down the growth of cancer cells without any side effects) from these phytochemicals.Many phytochemicals and their derived analogs have been identified as potential candidates for anticancer therapy.Effort has been made through this comprehensive review to highlight the recent developments and milestones achieved in cancer therapies using phytomolecules with their mechanism of action on nuclear and cellular factors.Furthermore,drags for cancer treatment and their limitations have also been discussed.

Cancer is a frightful disease and represents one of the biggest health-care issues for the human race and demands a proactive strategy for cure. Plants are reservoirs for novel chemical entities and provide a promising line for research on cancer. Hitherto, being effective, chemotherapy is accompanied by certain unbearable side effects. Nevertheless, plants and plant derived products is a revolutionizing field as these are Simple, safer, eco-friendly, low-cost, fast, and less toxic as compared with conventional treatment methods. Phytochemicals are selective in their functions and acts specifically on tumor cells without affecting normal cells. Carcinogenesis is complex phenomena that involves many signaling cascades. Phytochemicals are considered suitable candidates for anticancer drug development due to their pleiotropic actions on target events with multiple manners. The research is in progress for developing potential candidates (those can block or slow down the growth of cancer cells without any side effects) from these phytochemicals. Many phytochemicals and their derived analogs have been identified as potential candidates for anticancer therapy. Effort has been made through this comprehensive review to highlight the recent developments and milestones achieved in cancer therapies using phytomolecules with their mechanism of action on nuclear and cellular factors. Furthermore, drugs for cancer treatment and their limitations have also been discussed.

Toxoplasmosis is a protozoan disease that is caused by Toxoplasma gondii in livestock and humans. Due to its medical and veterinary importance, it is essential to study the seroprevalence of T. gondii infection among humans and animals in various parts of the world. The major objective of this study was to determine the seroprevalence and spatial distribution of toxoplasmosis in small ruminants (sheep and goats) of north-eastern region, Pakistan. A total of 1,000 animals comprising of sheep (n=470) and goats (n=530) were examined for T. gondii infection by using ELISA. An epidemiological data was collected in the form of questionnaire. A surface has been generated by using method of interpolation in Arc GIS with the help of IDW (inverse distance weight). The results showed higher seroprevalence of T. gondii in goats (42.8%) as compared to sheep (26.2%). The seroprevalence was higher in females as compared to males in all examined ruminants. Similarly, there is a wide variation in the seroprevalence of T. gondii in different breeds of sheep and goats showing higher seroprevalence in Teddy (52.8%) and Damani breed (34.5%) of goat and sheep's, respectively. The geographical and spatial distribution of T. gondii shows that it is widely distributed in different parts of the north-eastern region of Pakistan. Our results suggest widespread environmental contamination with T. gondii oocysts. It suggests us that small ruminants could be a potentially important source of T. gondii infection if their infected meat is consumed undercooked.
Animals ; Enzyme-Linked Immunosorbent Assay ; Female ; Goats* ; Humans ; Livestock ; Male ; Meat ; Methods ; Oocysts ; Pakistan* ; Ruminants ; Seroepidemiologic Studies* ; Sheep* ; Toxoplasma ; Toxoplasmosis*

AIM: To determine the clinical course and management of patients undergoing surgery for consecutive strabismus.METHODS: Patients less than 45 years of age presenting with consecutive strabismus were divided into two groups (1-Esodeviation and 2-Exodeviation). Angle of deviation was measured in prism diopter (PD). Conservative therapy was experienced during the course of follow-up after first surgery. All the subjects with deviation of more than 15PD after six months of follow-up were selected for repeat surgery. Compulsory investigations were performed. Secondary surgical procedures were performed under general anesthesia. Postoperative follow-up was done at 3 days, 15 days, 3 months and 6 months.RESULTS: Subjects(28.8%)developed consecutive stra-bismus within the study period. Second surgery on a dominant (fixating) eye in all patients was performed within 6 to 9 months after first surgery. After second surgical interven-tion, good surgical outcome was obtained and the tendency towards over correction was not observed in both groups during follow-up period.CONCLUSION: There is a need for guarded muscle correction during second surgery to avoid over corrections in future.

AIM:To evaluate the surgical outcome of congenital upper eyelid coloboma repair.METHODS:All patients underwent complete ophthalmic and general examination before going to surgery,and then examination under anesthesia was performed to assess the site and size of eyelid defect,conjunctival involvement.The status of cornea and ocular motility with forced duction test was also being noted.The surgical procedure was performed according to the size of defect.RESULTS:Out of 21 cases of congenital upper eyelid coloboma,18 occurred in isolation with upper eyelid medial defect,13 were bilateral and 5 were unilateral.Others were associated with Goldenhar syndrome and CHARGE syndrome with bilateral upper lid medial defects.All patients were presented for surgical corrections during age of 2.5-4.0 years except one that presented at 25 years of age.Cosmetically surgical results were acceptable,except one that was already presented with opaque corneal.CONCLUSION:In this study overall surgical results were satisfactory except one that was presented late with compromised cornea.