The antitumoral effect of the esculetin in HeLa cells through endoplasmic reticulum stress.

OBJECTIVE: Despite the multiple available treatment modalities, cervical cancer is one of the leading causes of mortality and morbidity among female gynecological cancers. Endoplasmic Reticulum (ER) is an effective organelle in ensuring cell homeostasis and is closely related to the development of cancer. Esculetin is a coumarin derivative that has anticancer, anti-inflammatory, antioxidant, and neuroprotective effects. Esculetin may have an anticancer effect by inducting apoptosis and ER stress. In this study, we evaluate that esculetin has an anti-tumor effect on human cervical cancer-derived (HeLa) cells via ER stress. MATERIALS AND METHODS: Esculetin was applied to the HeLa cells, and a viability test was performed using the methyl thiazolyl tetrazolium proliferation (MTT) assay. Expression levels of apoptotic genes and anti-apoptotic genes were determined by real-time polymerase chain reaction. The results were statistically evaluated. RESULTS: Analysis of the MTT assay detected that esculetin inhibited HeLa cell viability development. Based on Western blot and quantitative real-time polymerase chain reaction (qPCR) analyses, esculetin destroyed cervical cancer cells via the ER stress pathway. CONCLUSIONS: The results showed that esculetin may have a potent antitumoral effect. It can potentially be utilized in the pharmacological therapy of cervical cancer.

LncRNAs in necroptosis: Deciphering their role in cancer pathogenesis and therapy.

Necroptosis, a controlled type of cell death that is different from apoptosis, has become a key figure in the aetiology of cancer and offers a possible target for treatment. A growing number of biological activities, including necroptosis, have been linked to long noncoding RNAs (lncRNAs), a varied family of RNA molecules with limited capacity to code for proteins. The complex interactions between LncRNAs and important molecular effectors of necroptosis, including mixed lineage kinase domain-like pseudokinase (MLKL) and receptor-interacting protein kinase 3 (RIPK3), will be investigated. We will explore the many methods that LncRNAs use to affect necroptosis, including protein-protein interactions, transcriptional control, and post-transcriptional modification. Additionally, the deregulation of certain LncRNAs in different forms of cancer will be discussed, highlighting their dual function in influencing necroptotic processes as tumour suppressors and oncogenes. The goal of this study is to thoroughly examine the complex role that LncRNAs play in controlling necroptotic pathways and how that regulation affects the onset and spread of cancer. In the necroptosis for cancer treatment, this review will also provide insight into the possible therapeutic uses of targeting LncRNAs. Techniques utilising LncRNA-based medicines show promise in controlling necroptotic pathways to prevent cancer from spreading and improve the effectiveness of treatment.

Pyroptosis-related non-coding RNAs emerging players in atherosclerosis pathology.

Globally, atherosclerosis a persistent inflammatory condition of the artery walls continues to be the primary cause of cardiovascular illness and death. The ncRNAs are important regulators of important signalling pathways that affect pyroptosis and the inflammatory environment in atherosclerotic plaques. Comprehending the complex interaction between pyroptosis and non-coding RNAs (ncRNAs) offers fresh perspectives on putative therapeutic targets for ameliorating cardiovascular problems linked to atherosclerosis. The discovery of particular non-coding RNA signatures linked to the advancement of atherosclerosis could lead to the creation of novel biomarkers for risk assessment and customised treatment approaches. A thorough investigation of the regulatory networks regulated by these non-coding RNAs has been made possible by the combination of cutting-edge molecular methods and bioinformatics tools. Studying pyroptosis-related ncRNAs in detail appears to be a promising way to advance our understanding of disease pathophysiology and develop focused therapeutic methods as we work to unravel the complex molecular tapestry of atherosclerosis. This review explores the emerging significance of non-coding RNAs (ncRNAs) in the regulation of pyroptosis and their consequential impact on atherosclerosis pathology.

The dual role of MiR-210 in the aetiology of cancer: A focus on hypoxia-inducible factor signalling.

Tumorigenesis exemplifies the complex process of neoplasm origination, which is characterised by somatic genetic alterations and abnormal cellular growth. This multidimensional phenomenon transforms previously dormant cells into malignant equivalents, resulting in uncontrollable proliferation and clonal expansion. Various elements, including random mutations, harmful environmental substances, and genetic predispositions, influence tumorigenesis's aetiology. MicroRNAs (miRNAs) are now recognised as crucial determinants of gene expression and key players in several biological methods, including oncogenesis. A well-known hypoxia-inducible miRNA is MiR-210, which is of particular interest because of its complicated role in the aetiology of cancer and a variation of physiological and pathological situations. MiR-210 significantly impacts cancer by controlling the hypoxia-inducible factor (HIF) signalling pathway. By supporting angiogenesis, metabolic reprogramming, and cellular survival in hypoxic microenvironments, HIF signalling orchestrates adaptive responses, accelerating the unstoppable development of tumorous growth. Targeting several components of this cascade, including HIF-1, HIF-3, and FIH-1, MiR-210 plays a vital role in modifying HIF signalling and carefully controlling the HIF-mediated response and cellular fates in hypoxic environments. To understand the complexities of this relationship, careful investigation is required at the intersection of MiR-210 and HIF signalling. Understanding this relationship is crucial for uncovering the mechanisms underlying cancer aetiology and developing cutting-edge therapeutic approaches. The current review emphasises MiR-210's significance as a vital regulator of the HIF signalling cascade, with substantial implications spanning a range of tumor pathogenesis.

Non-coding RNAs (ncRNAs) and multidrug resistance in glioblastoma: Therapeutic challenges and opportunities.

Non-coding RNAs (ncRNAs) have been recognized as pivotal regulators of transcriptional and post-transcriptional gene modulation, exerting a profound influence on a diverse array of biological and pathological cascades, including the intricate mechanisms underlying tumorigenesis and the acquisition of drug resistance in neoplastic cells. Glioblastoma (GBM), recognized as the foremost and most aggressive neoplasm originating in the brain, is distinguished by its formidable resistance to the cytotoxic effects of chemotherapeutic agents and ionizing radiation. Recent years have witnessed an escalating interest in comprehending the involvement of ncRNAs, particularly lncRNAs, in GBM chemoresistance. LncRNAs, a subclass of ncRNAs, have been demonstrated as dynamic modulators of gene expression at the epigenetic, transcriptional, and post-transcriptional levels. Disruption in the regulation of lncRNAs has been observed across various human malignancies, including GBM, and has been linked with developing multidrug resistance (MDR) against standard chemotherapeutic agents. The potential of targeting specific ncRNAs or their downstream effectors to surmount chemoresistance is also critically evaluated, specifically focusing on ongoing preclinical and clinical investigations exploring ncRNA-based therapeutic strategies for glioblastoma. Nonetheless, targeting lncRNAs for therapeutic objectives presents hurdles, including overcoming the blood-brain barrier and the brief lifespan of oligonucleotide RNA molecules. Understanding the complex relationship between ncRNAs and the chemoresistance characteristic in glioblastoma provides valuable insights into the fundamental molecular mechanisms. It opens the path for the progression of innovative and effective therapeutic approaches to counter the therapeutic challenges posed by this aggressive brain tumor. This comprehensive review highlights the complex functions of diverse ncRNAs, including miRNAs, circRNAs, and lncRNAs, in mediating glioblastoma's chemoresistance.

Acute abdominal emergencies and spinal cord injury; our experiences: a retrospective clinical study.

STUDY DESIGN: Retrospective review of medical notes. OBJECTIVE: To describe clinical, laboratory and examination findings of acute abdominal emergencies (AAE) in Turkish patients with spinal cord injury (SCI) and to examine diagnosis and management of AAE in early stages. SETTING: Inpatient rehabilitation unit of tertiary research hospital. METHODS: The medical records of 237 SCI patients were reviewed. The SCI patients who were recruited in the study had been diagnosed with AAE and treated medically or surgically while they were inpatients at the rehabilitation clinic. RESULTS: Nine out of 237 SCI patients had been diagnosed with one of the AAE. Three patients were AIS A, three patients were AIS B and three patients were AIS C. The most common AAE was acute cholecystitis; three patients were diagnosed with this. The others were single cases of intra-abdominal hemorrhage, intra-abdominal abscess, tuba-ovarian abscess, subileus, Crohn's disease and cholangitis. Three of the patients were treated with surgery and six were treated medically. The most common symptoms in patients were fever, abdominal pain and abdominal discomfort (four of AAE). Three patients had abdominal tenderness and abdominal distension. The expected findings of AAE, rebound and defense, were positive only in two patients. CONCLUSION: Gall bladder disease is a common cause of AAE. The classic symptoms and examination findings will usually not facilitate acute abdomen diagnosis in the SCI group, so we should be aware of patients' subjective complaints and when necessary use advanced imaging techniques immediately.

Compliance with clean intermittent catheterization in spinal cord injury patients: a long-term follow-up study.

STUDY DESIGN: Retrospective review of medical notes. OBJECTIVE: To evaluate spinal cord injury (SCI) patients' compliance with bladder emptying method at long-term period after discharge and determine the frequency of urinary tract infections (UTIs). SETTING: Inpatient rehabilitation unit of tertiary research hospital. METHODS: Bladder management method of 164 new spinal cord injured patients were noted at discharge from rehabilitation center and follow-up. Patients were questioned whether they continued the initial bladder emtying method at follow-up, reasons for discontinuation and the history of treated UTIs. RESULTS: The most common bladder management method at discharge from inpatient rehabilitation center was clean intermittent catheterization (CIC) (63.4%). At follow-up 42% of the patients who used CIC changed their bladder emptying method. Rate of reverting to urethral indwelling catheter (IC) was 21.4%. Reasons for the patients who switched to IC application were recurrent UTIs, incontinence, nephrolithiasis, dependence on care givers and urethral strictures. For all patients, the frequency of treated UTI in 1 year was 38.8%. The number of UTIs were highest in patients using IC. CONCLUSION: Many factors, including urological complications, patient's preference, living environment, life-style and level of injury should be considered in deciding the method of bladder management in SCI patients. The CIC is a reliable and effective method in selected SCI patients. Despite changes in bladder emptying method, CIC was the most preferred method at long-term follow-up. Education of patients on catheterization technique and periodic follow-up is necessary to maintain patient compliance.

Comparison of mean platelet volume in patients with diabetes mellitus, impaired fasting glucose and non-diabetic subjects.

INTRODUCTION: Large platelets are more thrombogenic and thus put the patient at a higher risk status. Mean platelet volume (MPV) is a determinant of platelet functionality and increased MPV is associated with increased risk for myocardial infarction, stroke and transient ischaemic attacks. The objective of this study is to compare the MPV in patients with diabetes mellitus (DM), impaired fasting glucose (IFG), and non-diabetic controls. METHODS: This cross-sectional study was conducted at Dow University of Health Sciences, Karachi, Pakistan between the period of September 2006 and May 2007. Sample size of 204 in each group was calculated using power (1-beta) of 90 percent and level of significance (alpha) at five percent. Confirmed patients with DM, IFG and non-diabetic controls were selected and allocated to respective groups. A total of 612 patients were selected and allocated to three groups of 204 patients each, referred to as DM group, IFG group and non-DM group. Fasting blood glucose, platelet counts and MPV were done. RESULTS: Mean MPV in the DM group was 9.34 fl, in the IFG Group 8.98 fl, and in the non-DM group 8.63 fl. Comparison of MPV values for the three groups showed statistically significant intergroup and intragroup differences, with a p-value of 0.00. CONCLUSION: MPV was significantly increased in the IFG group, as compared to the non-DM group, and it increased further when compared to the DM and IFG groups.

Pelvic ganglioneuroma.

Ganglioneuroma is a rare benign neurogenic tumor originating from the sempathoadrenal nervous system and is considered the benign counterpart of neuroblastoma, lacking the immature neuroblastic cells. A case of pelvic ganglioneuroma is described.

Psychological distress among patients attending a general medical outpatient clinic in Pakistan.

It is not known whether the pattern of psychiatric disorders in medical outpatients in Pakistan is similar to that observed in the West. Consecutive medical outpatients completed the Self-Report Questionnaire (SRQ) to detect probable psychiatric disorder. The usual cut-off score of 8/9 was used. One-thousand and sixty-nine patients completed the SRQ (84% response rate) at four half-day clinics. Sixteen percent of men and 58% of women presented with medically unexplained symptoms. In men, 80% of patients with medically unexplained symptoms had an SRQ score of 9 or above (probable depressive disorder) compared to 40% of those with symptoms caused by recognized physical illness (P<.0005). In women, the respective proportions were 55.4% and 49.6% (P=.34). Depressive disorder is probably very common in medical outpatients in Pakistan, especially in men with medically unexplained symptoms. Systematic attempts to initiate antidepressant treatment in this setting should be attempted.

Recidivans cutaneous leishmaniasis unresponsive to liposomal amphotericin B (AmBisome).

A 60-year-old woman with thick crusted erythematous plaques on her glabella, apex nasi and left infraorbital region was diagnosed as recidivans cutaneous leishmaniasis. The lesions were resistant to antimonial drugs. Although some response was observed on the infraorbital region, lesions on the glabella and nose continued to infiltrate despite therapy with liposomal amphotericin B.

A novel mutation in the sterol 27-hydroxylase gene of a Pakistani family with autosomal recessive cerebrotendinous xanthomatosis.

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder of lipid storage with prominent neurologic features. The disease is associated with mutations in CYP27, which encodes mitochondrial sterol 27-hydroxylase, an enzyme that catalyzes the oxidation of sterol intermediates during bile acid synthesis. The loss of this enzyme results in accumulation of cholestanol in the nervous system and other tissues. Six different mutations have been previously described in CTX. We analyzed a Pakistani family, which included four affected individuals with clinical characteristics of CTX, for mutations in CYP27. The exons of CYP27 in the family DNA were amplified by polymerase chain reaction (PCR) and analyzed for mutations by band shifts (single stranded conformational polymorphism [SSCP]) and DNA sequencing. The PCR product for exon 4 showed an SSCP change in this family. The DNA of affected individuals showed an abnormal mobility pattern interpreted as homozygous for the mutation. One non-affected sibling was homozygous for the normal migrating pattern, whereas the parents and another non-affected sibling were heterozygous. The sequence of exon 4 of affected individuals showed a substitution of C to T in codon 237, thus substituting arginine to a stop codon. This mutation would terminate the translation, which may result in a protein half the size of the wild type rendering it practically inactive.

Oxygen desaturation during fiberoptic bronchoscopy.

A prospective study was performed to detect oxygen saturation (SaO2) during and following fiberoptic bronchoscopy (FOB) in 50 patients. Twenty-five patients (group 1) underwent the procedure without and 25 (group 2) with supplemental oxygen. The SaO2 declined from the baseline value of 96.4% to 92.08% in group 1 and to 94.88% in group 2 after bronchoscopy alone. The decline was also noted when biopsy and broncho-alveolar lavage (BAL) were performed, the lowest values being recorded during BAL. The result showed that the fall in SaO2 in group 2 was significantly less than that in group 1 (P < 0.05). SaO2 returned to baseline values after a mean time of 4.9 minutes in group 1 and 2.4 minutes in group 2, demonstrating the benefit of supplemental oxygen.

Enoxacin in the treatment of typhoid fever.

Enoxacin 400 mg twice daily was given orally to 40 patients who had Salmonella typhi- or Salmonella paratyphi-positive blood or bone marrow cultures. One patient was switched to parenteral therapy within 48 hours of study enrollment, but the remaining 39 patients were given enoxacin for 10 to 14 days. All 39 patients were cured by enoxacin, even though 23 (58.9%) strains were resistant to cotrimoxazole and 16 (41%) strains were multiply resistant to ampicillin, chloramphenicol, and cotrimoxazole. No adverse events necessitated the interruption of therapy. In this study, enoxacin was well tolerated and efficacious in the treatment of typhoid fever.