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Lamins, which are crucial type V intermediate filament proteins found in the nuclear lamina, are essential for maintaining the stability and function of the nucleus in higher vertebrates. They are classified into A- and B-types, and their distinct expression patterns contribute to cellular survival, development, and functionality. Lamins emerged during the transition from open to closed mitosis, with their complexity increasing alongside organism evolution. Derived from the LMNA, LMNB1, and LMNB2 genes, lamins undergo alternative splicing to produce seven variants, influencing cellular processes such as stiffness, chromatin condensation, and cell cycle regulation. The lamin network interacts with the cytoskeleton via Linkers of the nucleoskeleton to the cytoskeleton (LINC) complexes, playing a critical role in cellular stability and mechanotransduction. Lamins also regulate active transport into and out of the nucleus, affecting nuclear integrity, positioning, DNA maintenance, and gene expression. Genetic mutations in lamin genes lead to laminopathies, highlighting their functional significance and organizational roles. Changes in lamin subtype composition within the nuclear lamina have significant implications for cancer development, impacting cellular stiffness, mobility, and the Epithelial-to-Mesenchymal Transition (EMT). Lamin A/C, in particular, plays multifaceted roles in cancer biology, influencing progression, metastasis, and therapy response through interactions with various proteins and pathways. Dysregulated lamin expression is commonly observed in cancers, suggesting their potential as diagnostic and prognostic markers. This chapter underscores the pivotal roles of lamins in nuclear architecture and cancer biology, emphasizing their impact on cellular functions and disease pathology. Understanding lamin behavior and regulation mechanisms holds promise for developing novel diagnostic tools and targeted therapies in cancer treatment., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2025. Published by Elsevier Inc.)

Regulated cell division is one of the fundamental phenomena which is the basis of all life on earth. Even a single base pair mutation in DNA leads to the production of the dysregulated protein that can have catastrophic consequences. Cell division is tightly controlled and orchestrated by proteins called cyclins and cyclin-dependent kinase (CDKs), which serve as licensing factors during different phases of cell division. Dysregulated cell division is one of the most important hallmarks of cancer and is commonly associated with a mutation in cyclins and CDKs along with tumor suppressor proteins. Therefore, targeting the component of the cell cycle which leads to these characteristics would be an effective strategy for treating cancers. Specifically, Cyclin-dependent kinases (CDKs) involved in cell cycle regulation have been identified to be overexpressed in many cancers. Many studies indicate that oncogenesis occurs in cancerous cells by the overactivity of different CDKs, which impact cell cycle progression and checkpoint dysregulation which is responsible for development of tumor. The development of CDK inhibitors has emerged as a promising and novel approach for cancer treatment in both solid and hematological malignancies. Some of the novel CDK inhibitors have shown remarkable results in clinical trials, such as-Ribociclib®, Palbociclib® and Abemaciclib®, which are CDK4/6 inhibitors and have received FDA approval for the treatment of breast cancer. In this chapter, we discuss the molecular mechanism through which cyclins and CDKs regulate cell cycle progression and the emergence of cyclins and CDKs as rational targets in cancer. We also discuss recent advances in developing CDK inhibitors, which have emerged as a novel class of inhibitors, and their associated toxicities in recent years., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A new highly green luminescent binuclear palladium 2-pyrazinecarboxamide-bipyridine complex [Pd(pyc)(bpy)] was prepared and characterized. The binuclear Pd(pyc)(bpy) complex doped in sol-gel matrix has a strong luminescence intensity at 547 nm with λ ex = 330 nm in water The method depends on the quenching of the luminescence intensity of the binuclear Pd(pyc)(bpy) complex at 547 nm by different concentrations of uric acid. The remarkable quenching of the luminescence intensity of the binuclear Pd(pyc)(bpy) complex, doped in a sol-gel matrix, by uric acid was successfully used for the determination of uric acid in serum samples of patients with hypouricemia disease. The calibration plot was achieved over the concentration 3.9 × 10 -9 to 1.2 × 10 -4 mol L -1 uric acid with a correlation coefficient of 0.9 and a detection limit of 1.8 × 10 -10 mol L -1 . The method was used satisfactorily for the assessment of the uric acid in a number of serum samples collected from various patients with Hypouricemia disease., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Delayed brain development in perinatally HIV-infected children may affect the functional brain activity and subsequently cognitive function. The current study evaluated the functional brain activity in HIV-infected children by quantifying the amplitude of low frequency fluctuations (ALFF) and functional connectivity (FC). Additionally, correlation of ALFF and FC with cognitive measures was performed. Twenty-six HIV-infected children and 20 control children underwent neuropsychological (NP) assessment and resting-state functional magnetic resonance imaging (rs-fMRI). ALFF and FC maps were generated and group differences were analyzed using two-sample t-test. Furthermore, ALFF and FC showing significant group differences were correlated with NP scores using Pearson's correlation. Significantly lower ALFF in the left middle temporal gyrus, precentral and post central gyrus was observed in HIV-infected children compared to controls. FC was significantly reduced in the right inferior parietal, vermis, middle temporal and left postcentral regions, and significantly increased in the right precuneus, superior parietal and left middle frontal regions in HIV-infected children as compared to control. HIV-infected children showed significantly lower NP scores in various domains including closure, exclusion, memory, verbal meaning, quantity and hidden figure than controls. These waning cognitive functions were significantly associated with changes in ALFF and FC in HIV-infected children. The findings suggest that abnormal ALFF and FC may responsible for cognitive deficits in HIV-infected children. ALFF and FC in association with cognitive evaluation may provide a clinical biomarker to evaluate functional brain activity and to plan neurocognitive intervention in HIV-infected children undergoing standard treatment., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Pediatric HIV patients often suffer with neurodevelopmental delay and subsequently cognitive impairment. While tissue injury in cortical and subcortical regions in the brain of adult HIV patients has been well reported there is sparse knowledge about these changes in perinatally HIV infected pediatric patients. We analyzed cortical thickness, subcortical volume, structural connectivity, and neurocognitive functions in pediatric HIV patients and compared with those of pediatric healthy controls. With informed consent, 34 perinatally infected pediatric HIV patients and 32 age and gender matched pediatric healthy controls underwent neurocognitive assessment and brain magnetic resonance imaging (MRI) on a 3 T clinical scanner. Altered cortical thickness, subcortical volumes, and abnormal neuropsychological test scores were observed in pediatric HIV patients. The structural network connectivity analysis depicted lower connection strengths, lower clustering coefficients, and higher path length in pediatric HIV patients than healthy controls. The network betweenness and network hubs in cortico-limbic regions were distorted in pediatric HIV patients. The findings suggest that altered cortical and subcortical structures and regional brain connectivity in pediatric HIV patients may contribute to deficits in their neurocognitive functions. Further, longitudinal studies are required for better understanding of the effect of HIV pathogenesis on brain structural changes throughout the brain development process under standard ART treatment.

Macrocyclic lactones (ML) are important anthelmintics used in animals and humans against parasite nematodes, but their therapeutic success is compromised by the spread of ML resistance. Some ABC transporters, such as p-glycoproteins (Pgps), are selected and overexpressed in ML-resistant nematodes, supporting a role for some drug efflux proteins in ML resistance. However, the role of such proteins in ML transport remains to be clarified at the molecular level. Recently, Caenorhabditis elegans Pgp-1 (Cel-Pgp-1) has been crystallized, and its drug-modulated ATPase function characterized in vitro revealed Cel-Pgp-1 as a multidrug transporter. Using this crystal structure, we have developed an in silico drug docking model in order to study the binding of ML and other anthelmintic drugs to Cel-Pgp-1. All tested ML bound with high affinity in a unique site, within the inner chamber of the protein, supporting that ML may be transported by Cel-Pgp-1. Interestingly, interacting residues delineate a ML specific fingerprint involving H-bonds, including T1028. In particular, benzofurane and spiroketal moieties bound to specific sub-sites. When compared with the aglycone ML, such as moxidectin and ivermectin aglycone, avermectin anthelmintics have significant higher affinity for Cel-Pgp-1, likely due to the sugar substituent(s) that bind to a specific area involving H-bonds at Y771. Triclabendazole, closantel and emodepside bound with good affinities to different sub-sites in the inner chamber, partially overlapping with the ML binding site, suggesting that they could compete for Cel-Pgp-1-mediated ML transport. In conclusion, this work provides novel information on the role of nematode Pgps in transporting anthelmintics, and a valuable tool to predict drug-drug interactions and to rationally design new competitive inhibitors of clinically-relevant nematode Pgps, to improve anthelmintic therapeutics., (Copyright © 2016. Published by Elsevier Ltd.)

Aim: Adequate lymph node resection in rectal cancer is important for staging and local control. This study aims to verify the effect of neoadjuvant chemoradiation, as well as some clinicopathological features, on the yield of lymph nodes in rectal carcinoma., Methods: Data on consecutive patients who had total mesorectal excision for rectal adenocarcinoma at a single cancer center between January 2003 and July 2008 were reviewed. No patient had any prior pelvic surgery or radiotherapy. Patients had neoadjuvant chemoradiotherapy if they were stage II or III., Results: A total of 116 patients were included. The mean age was 53 years (range 29-83). Fifty-nine patients (51%) received neoadjuvant therapy before resection. The mean number of lymph nodes removed was 18 (range 4-67) per specimen. There was less lymph node yield in patients who received neoadjuvant therapy (16 vs. 19, p = 0.008). Only 64% of patients who had preoperative therapy had 12 lymph nodes or more in the specimen as opposed to 88% of those who had surgery upfront (p = 0.003). Other factors associated with lower lymph node yield included: female sex (p = 0.03) and tumour location in the lower rectum (p = 0.002). Age, tumour stage and grade, type of operation and surgical delay did not affect the number of lymph nodes removed., Conclusion: Preoperative chemoradiotherapy for rectal cancer results in reduction in lymph node yield. Female sex and lower rectal tumours are also associated with retrieval of fewer lymph nodes., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Global and specific cognitive functions were assessed in 57 patients with ischemic strokes subjected to clinical neuropsychiatric, psychometric, electrophysiological and cranial tomographic evaluation. Patients did significantly worse than normal controls in the Blessed dementia scale, Sandoz clinical assessment geriatric scale but not the Folstein mini-mental state examination. Of the specific cognitive functions, attention and psychomotor performance were significantly impaired in stroke patients when compared to normal controls. The impairment in global cognitive functions, attention and psychomotor performance was more evident in chronic than acute cases. Increasing age correlated positively to the deterioration in psychomotor performance and perception. Cranial tomographic size of infarction was significantly related to global cognitive as well as intentional (sensory) memory impairment. The more marked the conventional electroencephalographic abnormalities, the more impaired were the global cognitive functions. High limit of the theta percent power correlated positively to deterioration in psychomotor performance. All P300 parameters except amplitude correlated significantly with impairment of global cognitive function and psychomotor performance in stroke patients.

A study was carried out to examine aspects of the health status of children from a group of 'travelling people' in Northern Ireland. A total of 350 children, aged under 16 years, were included in the study. Data were gathered by community health doctors and health visitors using a standardised questionnaire. The study revealed that this community has a high degree of consanguinity and points to higher levels of congenital abnormalities than in the settled community. Uptake of immunisation was less than the settled community and hospital admissions in the younger age group were particularly due to infectious diseases. The authors conclude that provision of health services for travelling people in Northern Ireland should be urgently reviewed with consideration of the needs and lifestyle of this group. The provision of suitable sites for travelling people with adequate water and sewage facilities to reduce potential risks to health is also advocated.