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1.
Heliyon ; 10(6): e28038, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38524534

RESUMO

Herbal medicinal plants have been used for centuries in traditional medicine, and it is interesting to see how modern research has identified the active compounds responsible for their therapeutic effects. The green synthesis of silver nanoparticles using herbal medicinal plants, such as Swertia chirata, is particularly noteworthy due to its antimicrobial properties. In the current study, the Swertia chirata plant was collected for the first time from the region of Murree, Punjab, Pakistan. After collection, extracts were prepared in different solvents (ethanol, methanol, chloroform, and distilled water), and silver nanoparticles were synthesized by reducing silver nitrate (AgNO3). The UV-visible spectrophotometer, SEM, and EDX were used to characterize the synthesized nanoparticles in terms of their size and shape. The phytochemical analysis of crude extract was performed to determine the presence of different kinds of phytochemicals. The antibacterial activity of plant extracts and the silver nanoparticles were then assessed using the agar well diffusion method against various pathogenic bacteria. The results showed that the plant contains several phytochemicals with remarkable antioxidant potential. The antibacterial analysis revealed that silver nanoparticles and the plant extracts exhibited a significant zone of inhibition against human pathogenic bacteria (Escherichia coli, S. capitis, B. subtilis, and Pseudomonas aeruginosa) as compared to the cefixime and norfloxacin. This implies that the nanoparticles have the potential to be used in nano-medicine applications, such as drug delivery systems, as well as for their antibacterial, antifungal, and antiviral activities. Additionally, the development and application of materials and technologies at the nanometer scale opens possibilities for the creation of novel drugs and therapies. Overall, the study highlights the promising potential of herbal medicinal plants found in Murree, Punjab, Pakistan, and green-synthesized silver nanoparticles in various fields of medicine and nanotechnology.

2.
Sci Rep ; 14(1): 6333, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491048

RESUMO

Precisely measuring pressure in microfluidic flows is essential for flow control, fluid characterization, and monitoring, but faces specific challenges such as achieving sufficient resolution, non-invasiveness, or ease of use. Here, we demonstrate a fully integrated multiplexed optofluidic pressure sensor, entirely decoupled from the flow path, that enables local pressure measurements along any microfluidic channel without altering its flow geometry. The sensor itself relies on the compression of a soft mechano-actuated hydrogel, changing color in response to a pressure change. The hydrogel is separated from the fluid circulating in the channel by a thin membrane, allowing for the unrestricted use of different types of fluids. Imaging the gel through the transparent PDMS with a color camera provides a direct, easy, and contact-free determination of the fluid pressure at the sensing location for pressures as small as 20mbar with a resolution of around 10mbar. The sensitivity and accessible pressure range can be tuned via the mechanical properties of the sensing unit. The photonic gel can also be used to acquire 2D pressure or deformation maps, taking advantage of the fast response time and fine spatial resolution.

3.
Front Mol Neurosci ; 17: 1222935, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495551

RESUMO

This study reports on biallelic homozygous and monoallelic de novo variants in SLITRK3 in three unrelated families presenting with epileptic encephalopathy associated with a broad neurological involvement characterized by microcephaly, intellectual disability, seizures, and global developmental delay. SLITRK3 encodes for a transmembrane protein that is involved in controlling neurite outgrowth and inhibitory synapse development and that has an important role in brain function and neurological diseases. Using primary cultures of hippocampal neurons carrying patients' SLITRK3 variants and in combination with electrophysiology, we demonstrate that recessive variants are loss-of-function alleles. Immunostaining experiments in HEK-293 cells showed that human variants C566R and E606X change SLITRK3 protein expression patterns on the cell surface, resulting in highly accumulating defective proteins in the Golgi apparatus. By analyzing the development and phenotype of SLITRK3 KO (SLITRK3-/-) mice, the study shows evidence of enhanced susceptibility to pentylenetetrazole-induced seizure with the appearance of spontaneous epileptiform EEG as well as developmental deficits such as higher motor activities and reduced parvalbumin interneurons. Taken together, the results exhibit impaired development of the peripheral and central nervous system and support a conserved role of this transmembrane protein in neurological function. The study delineates an emerging spectrum of human core synaptopathies caused by variants in genes that encode SLITRK proteins and essential regulatory components of the synaptic machinery. The hallmark of these disorders is impaired postsynaptic neurotransmission at nerve terminals; an impaired neurotransmission resulting in a wide array of (often overlapping) clinical features, including neurodevelopmental impairment, weakness, seizures, and abnormal movements. The genetic synaptopathy caused by SLITRK3 mutations highlights the key roles of this gene in human brain development and function.

4.
Inquiry ; 61: 469580241237106, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38462886

RESUMO

The relationship between women's working status and fertility behavior has been a topic of interest for researchers and policymakers. The societal shifts over time, particularly the increasing participation of women in the workforce, have transformed traditional roles. Women, once primarily perceived as caregivers, are now assuming roles of economic independence. This transformation prompts a re-evaluation of the traditional association between women's working status and fertility behavior. This study aims to investigate the impact of women's working status on fertility behavior using a multistage stratified sampling design. A total of 408 women aged 15 to 49 years were recruited from 2 strata: working and non-working women. The data were collected through face-to-face interviews using a structured questionnaire. Descriptive statistics, cluster analysis, and generalized additive models were used for in-depth analysis of the dataset. An examination of fertility patterns indicates that, on average, working women bear 2.90 live children, while their non-working counterparts have an average of 3.52 children. Stillbirth was reported in 13% of housewives and 15.1% of working women. However, further analysis revealed that the relationship between women's employment status and fertility behavior varied depending on Social and Cultural Norms, Reproductive Rights, Workplace Policies, Economic Independence, Age, and Life Stage. Our findings suggest that promoting access to family-friendly policies and services, as well as challenging gender norms and cultural values, could help address the impact of women's employment on fertility behavior.


Assuntos
Fertilidade , Classe Social , Criança , Feminino , Humanos , Fatores Socioeconômicos , Dinâmica Populacional , Paquistão , Demografia , Escolaridade
6.
J Med Case Rep ; 18(1): 86, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38438911

RESUMO

BACKGROUND: Peutz-Jeghers syndrome is a rare hereditary condition characterized by gastrointestinal polyps and pigmented oral lesions. The case contributes to a deeper understanding of Peutz-Jeghers syndrome and underscores the significance of interdisciplinary collaboration for accurate diagnosis and tailored therapeutic strategies. CASE DESCRIPTION: We present a case of a 15-year-old Afghan female patient with multiple polyps throughout the gastrointestinal tract and mucocutaneous pigmentation. Despite previous medical visits and colonoscopies, her symptoms persisted. A multidisciplinary team discussed the case and recommended further investigations and interventions. A polypectomy was performed, confirming the presence of hamartomatous polyps. The patient was diagnosed with Peutz-Jeghers syndrome, but during the course of treatment she went through complications and was managed surgically as well. CONCLUSION: Timely polyp removal and lifelong surveillance are crucial in managing Peutz-Jeghers syndrome. Further research and genetic analysis are needed to improve understanding and management of this rare disorder.


Assuntos
Síndrome de Peutz-Jeghers , Pólipos , Feminino , Humanos , Adolescente , Síndrome de Peutz-Jeghers/complicações , Síndrome de Peutz-Jeghers/diagnóstico , Síndrome de Peutz-Jeghers/cirurgia , Estômago , Duodeno , Intestino Grosso
8.
Food Chem Toxicol ; 187: 114586, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38493978

RESUMO

The risk assessment of heavy metals in tea is extremely imperative for the health of tea consumers. However, the effects of varietal variations and seasonal fluctuations on heavy metals and minerals in tea plants remain unclear. Inductively coupled plasma optical emission spectrometry (ICP-OES) was used to evaluate the contents of aluminum (Al), manganese (Mn), magnesium (Mg), boron (B), calcium (Ca), copper (Cu), cobalt (Co), iron (Fe), sodium (Na), zinc (Zn), arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), and antimony (Sb) in the two categories of young leaves (YL) and mature leaves (ML) of tea (Camellia sinensis) cultivars throughout the growing seasons. The results showed significant variations in the contents of the investigated nutrients both among the different cultivars and growing seasons as well. Furthermore, the average concentrations of Al, Mn, Mg, B, Ca, Cu, Co, Fe, Na, Zn, As, Cd, Cr, Ni, and Sb in YL ranged, from 671.58-2209.12, 1260.58-1902.21, 2290.56-2995.36, 91.18-164.68, 821.95-5708.20, 2.55-3.80, 3.96-25.22, 37.95-202.84, 81.79-205.05, 27.10-69.67, 0.028-0.053, 0.065-0.127, 2.40-3.73, 10.57-12.64, 0.11-0.14 mg kg-1, respectively. In ML, the concentrations were 2626.41-7834.60, 3980.82-6473.64, 3335.38-4537.48, 327.33-501.70, 9619.89-13153.68, 4.23-8.18, 17.23-34.20, 329.39-567.19, 145.36-248.69, 40.50-81.42, 0.089-0.169, 0.23-0.27, 5.24-7.89, 18.51-23.97, 0.15-0.19 mg kg-1, respectively. The contents of all analyzed nutrients were found to be higher in ML than in YL. Target hazard quotients (THQ) of As, Cd, Cr, Ni, and Sb, as well as the hazard index (HI), were all less than one, suggesting no risk to human health via tea consumption. This research might provide the groundwork for essential minerals recommendations, as well as a better understanding and management of heavy metal risks in tea.


Assuntos
Arsênio , Camellia sinensis , Metais Pesados , Humanos , Estações do Ano , Cádmio/análise , Monitoramento Ambiental/métodos , Metais Pesados/toxicidade , Metais Pesados/análise , Arsênio/análise , Minerais , Cromo/análise , Níquel/análise , Manganês/análise , Alumínio/análise , Medição de Risco , Zinco/análise , Chá/química
9.
Epilepsy Res ; 201: 107283, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38382230

RESUMO

Progressive myoclonic epilepsies (PMEs) are a group of neurodegenerative disorders, predominantly affecting adolescents and, characterized by generalized worsening myoclonus epilepsies, ataxia, cognitive deficits, and dementia. To date, several genes, having implications in diverse phenotypic expressions associated with PMEs, have been identified. Genetic diagnosis is available for most of the adolescence-onset myoclonic epilepsies. This study aimed to elucidate the genetic basis of PMEs in three multiplex Pakistani families exhibiting clinically variable phenotypes. Causative variant(s) in the studied families, and mode of segregation were identified by Whole Exome Sequencing (WES) of the probands, followed by bi-directional Sanger sequencing for final validation. We identified homozygous recessive CLN6 missense variant c.768 C>G (p.Asp256Glu) in Family 1, and c.889 C>A (p.Pro297Thr) variant in Family 2. While in Family 3, we found a homozygous variant (c.316dup) that caused a frameshift mutation, leading to a premature stop codon in the CLN6 protein, resulting in a truncated protein (p.Arg106ProfsTer26). Though CLN6 is previously identified to underlie late infantile and adolescent onset neuronal ceroid lipofuscinosis, this study supports and expands the phenotypic spectrum of CLN6 mutations and signifies diagnositc potential CLN6 variants for PMEs. Diverse pathological effects of variant c .768 C>G were observed in Family 1, with same genotypes, suggesting clinical heterogeneity and/or variable expressivity that might be the implication of pleiotropic effects of the gene in these cases.

10.
Sci Rep ; 14(1): 2868, 2024 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-38311636

RESUMO

The escalating presence of heavy metals (HMs) in the Panjkora River water and their impact on fish pose a significant challenge to both the ecological community and human health. Consequently, a study was conducted with the primary aim of elucidating their influence on human health-related issues. To address this, the concentrations of heavy metals, including arsenic (As), cadmium (Cd), iron (Fe), manganese (Mn), lead (Pb), and zinc (Zn), in both water and the fish species Crossocheilus diplocheilus were investigated across various locations within the study area. The quantification of HMs concentration was carried out utilizing an atomic absorption spectrophotometer. The highest concentration in water was found as 0.060 mg/L for Pb and lowest for Fe, whereas the highest concentration in fish was 2.028 mg/kg for Pb and lowest for As. Human health risk associated with fish eating was evaluated by using health risk indices (HRI) for non-carcinogenic health risks and targeted cancer risk (TR) for carcinogenic health risks. The values of the health risk index (HRI) were found greater than 1 except Fe (0.0792), Zn (0.782), and Mn (0.541). The highest mean HRI > 1 was recorded for As (62.99), Cd (26.85), and Pb (10.56). This implies that fish consumption from river Panjkora is not safe up to some extent. Similarly, the TR value for As, Cd, and Pb was found 2.8 [Formula: see text], 1.6 [Formula: see text], 2.8 ×[Formula: see text] which showed cancer risk. There is a detected risk to human health associated with the consumption of fish from the Panjkora River. The government must implement adaptive measures to address this significant issue of water pollution in the study area. Additionally, there is a need for further extensive and prolonged research studies in this context.


Assuntos
Arsênio , Metais Pesados , Neoplasias , Poluentes Químicos da Água , Animais , Humanos , Qualidade da Água , Cádmio , Chumbo , Monitoramento Ambiental , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Metais Pesados/toxicidade , Metais Pesados/análise , Arsênio/toxicidade , Arsênio/análise , Manganês , Rios , Peixes , Medição de Risco
11.
Pathogens ; 13(2)2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38392880

RESUMO

Acanthamoeba keratitis (AK) is a severe, rare protozoal infection of the cornea. Acanthamoeba can survive in diverse habitats and at extreme temperatures. AK is mostly seen in contact lens wearers whose lenses have become contaminated or who have a history of water exposure, and in those without contact lens wear who have experienced recent eye trauma involving contaminated soil or water. Infection usually results in severe eye pain, photophobia, inflammation, and corneal epithelial defects. The pathophysiology of this infection is multifactorial, including the production of cytotoxic proteases by Acanthamoeba that degrades the corneal epithelial basement membrane and induces the death of ocular surface cells, resulting in degradation of the collagen-rich corneal stroma. AK can be prevented by avoiding risk factors, which includes avoiding water contact, such as swimming or showering in contact lenses, and wearing protective goggles when working on the land. AK is mostly treated with an antimicrobial therapy of biguanides alone or in combination with diaminidines, although the commercial availability of these medicines is variable. Other than anti-amoeba therapies, targeting host immune pathways in Acanthamoeba disease may lead to the development of vaccines or antibody therapeutics which could transform the management of AK.

13.
Sci Total Environ ; 915: 170145, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38242478

RESUMO

Insect pollinators, vital for agriculture and biodiversity, face escalating threats from climate change. We argue and explore the pivotal role of the microbiomes in shaping adaptations of insect pollinator resilience amid climate-induced challenges (climate change and habitat alteration). Examining diverse taxonomic groups, we unravel the interplay between insect physiology, microbiomes, and adaptive mechanisms. Climate-driven alterations in microbiomes impact insect health, behavior, and plant interactions, posing significant effects on agricultural ecosystems. We propose harnessing microbiome-mediated adaptations as a strategic approach to mitigate climate change impacts on crop pollination. Insights into insect-pollinator microbiomes offer transformative avenues for sustainable agriculture, including probiotic interventions (use of EM PROBIOTIC) and microbiome engineering (such as engineering gut bacteria) to induce immune responses and enhanced pollination services. Integrating microbiome insights into conservation practices elucidates strategies for preserving pollinator habitats, optimizing agricultural landscapes, and developing policies to safeguard pollinator health in the face of environmental changes. Finally, we stress interdisciplinary collaboration and the urgency of understanding pollinator microbiome dynamics under climate change in future research.


Assuntos
Ecossistema , Microbiota , Animais , Abelhas , Polinização/fisiologia , Mudança Climática , Insetos , Biodiversidade
14.
Brain ; 147(4): 1197-1205, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38141063

RESUMO

Dysfunctional RNA processing caused by genetic defects in RNA processing enzymes has a profound impact on the nervous system, resulting in neurodevelopmental conditions. We characterized a recessive neurological disorder in 18 children and young adults from 10 independent families typified by intellectual disability, motor developmental delay and gait disturbance. In some patients peripheral neuropathy, corpus callosum abnormalities and progressive basal ganglia deposits were present. The disorder is associated with rare variants in NUDT2, a mRNA decapping and Ap4A hydrolysing enzyme, including novel missense and in-frame deletion variants. We show that these NUDT2 variants lead to a marked loss of enzymatic activity, strongly implicating loss of NUDT2 function as the cause of the disorder. NUDT2-deficient patient fibroblasts exhibit a markedly altered transcriptome, accompanied by changes in mRNA half-life and stability. Amongst the most up-regulated mRNAs in NUDT2-deficient cells, we identified host response and interferon-responsive genes. Importantly, add-back experiments using an Ap4A hydrolase defective in mRNA decapping highlighted loss of NUDT2 decapping as the activity implicated in altered mRNA homeostasis. Our results confirm that reduction or loss of NUDT2 hydrolase activity is associated with a neurological disease, highlighting the importance of a physiologically balanced mRNA processing machinery for neuronal development and homeostasis.


Assuntos
Deficiência Intelectual , Transtornos do Neurodesenvolvimento , Criança , Adulto Jovem , Humanos , RNA Mensageiro/genética , Monoéster Fosfórico Hidrolases/genética , Transtornos do Neurodesenvolvimento/genética , Deficiência Intelectual/genética , 60536
15.
Planta ; 259(1): 18, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38085368

RESUMO

MAIN CONCLUSION: Lead disrupts plant metabolic homeostasis and key structural elements. Utilizing modern biotechnology tools, it's feasible to develop Pb-tolerant varieties by discovering biological players regulating plant metabolic pathways under stress. Lead (Pb) has been used for a variety of purposes since antiquity despite its toxic nature. After arsenic, lead is the most hazardous heavy metal without any known beneficial role in the biological system. It is a crucial inorganic pollutant that affects plant biochemical and morpho-physiological attributes. Lead toxicity harms plants throughout their life cycle and the extent of damage depends on the concentration and duration of exposure. Higher levels of lead exposure disrupt numerous key metabolic activities of plants including oxygen-evolving complex, organelles integrity, photosystem II connectivity, and electron transport chain. This review summarizes the detrimental effects of lead toxicity on seed germination, crop growth, and yield, oxidative and ultra-structural alterations, as well as nutrient absorption, transport, and assimilation. Further, it discusses the Pb-induced toxic modulation of stomatal conductance, photosynthesis, respiration, metabolic-enzymatic activity, osmolytes accumulation, and antioxidant activity. It is a comprehensive review that reports on omics-based studies along with morpho-physiological and biochemical modifications caused by lead stress. With advances in DNA sequencing technologies, genomics and transcriptomics are gradually becoming popular for studying Pb stress effects in plants. Proteomics and metabolomics are still underrated and there is a scarcity of published data, and this review highlights both their technical and research gaps. Besides, there is also a discussion on how the integration of omics with bioinformatics and the use of the latest biotechnological tools can aid in developing Pb-tolerant crops. The review concludes with core challenges and research directions that need to be addressed soon.


Assuntos
Chumbo , Poluentes do Solo , Chumbo/toxicidade , Multiômica , Poluentes do Solo/metabolismo , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Biologia Computacional
16.
Plants (Basel) ; 12(24)2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38140419

RESUMO

Globally, maize is one of the most consumed crops along with rice and wheat. However, maize is sensitive to different abiotic stress factors, such as drought, which have a significant impact on its production. The aims of this study were to investigate (1) genetic variation among 41 maize-inbred lines and the relationships among them and (2) significant marker-trait associations (SMTAs) between 7 selected physiochemical traits and 200 simple sequence repeat (SSR) markers to examine the genetics of these traits. A total of 1023 alleles were identified among the 41 maize-inbred lines using the 200 SSR loci, with a mean of 5.1 alleles per locus. The average major allele frequency, gene diversity, and polymorphism information content were 0.498, 0.627, and 0.579, respectively. The population structure analysis based on the 200 SSR loci divided the maize germplasm into two primary groups with an admixed group. Moreover, this study identified, respectively, 85 SMTAs and 31 SMTAs using a general linear model (Q GLM) and a mixed linear model (Q + K MLM) with statistically significant (p < 0.05 and <0.01) associations with the seven physiochemical traits (caffeic acid content, chlorogenic acid content, gallic acid content, ferulic acid content, 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity, leaf relative moisture content, total phenolic content). These SSR markers were highly correlated with one or more of the seven physiochemical traits. This study provides insights into the genetics of the 41 maize-inbred lines and their seven physiochemical traits and will be of assistance to breeders in the marker-assisted selection of maize for breeding programs.

17.
J Orthop Res ; 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37975261

RESUMO

Adjacent segment degeneration is commonly observed in patients after fusion surgery. Among the associated risk factors is the preoperative presence of adjacent disc degeneration (ADD). The risk factors and other spine phenotypes associated with preoperative ADD is critical to understand the pathological process and better prognosis postsurgery. Current study aims to assess and compare the magnetic resonance imaging (MRI) spinal phenotype of herniated level with and without ADD. Preoperative T2W sagittal lumbar MRI images of 155 lumbar disc herniated patients were analyzed for the presence of ADD (Pfirrmann grade III and above). The herniated disc level was assessed for the presence and absence of vertebral endplate (VEP) defects, Modic changes, and high intensity zone (HIZ). Mean age of patients was 38 ± 2 years, almost 62% were males. ADD was found in 57%, VEP defects were seen in 62% of the herniated level, 24.5% showed Modic changes, 3.8% showed spondylolishthesis, and 15.5% revealed HIZ. Age and other demographic factors did not have any significant effect on the presence of ADD, the patients with extruded and sequestered discs had more ADD (p = 0.02). VEP defects were significantly higher in levels with ADD (p = 0.02). Patients with ADD had significantly VEP defect scores (p = 0.01), Modic score (p = 0.002), HIZ score (0.02), and posterior bulge score (p < 0.001). Findings suggest that affected levels with VEP defects and severe grade of disc herniation have the greater likelihood of having ADD. Once developed this ADD may also affect the other spinal levels, and also can affect postoperative prognosis.

18.
Brain ; 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37951597

RESUMO

The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins, and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Utilizing exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with YnMyr chemical proteomics in the model organisms and human cells, with the latter also being subjected further to ACBD6 peroxisomal localization studies. The affected individuals (23 males and 22 females), with ages ranging from 1 to 50 years old, typically present with a complex and progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) with significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%), and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia (76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%), microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement disorder was dystonia (94%), frequently leading to early-onset progressive postural deformities (97%), limb dystonia (55%), and cervical dystonia (31%). A jerky tremor in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing with advancing age (32%), and simple motor and vocal tics were among other frequent movement disorders. Midline brain malformations including corpus callosum abnormalities (70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and small inferior cerebellar vermis (38% each), as well as hypertrophy of the clava (24%) were common neuroimaging findings. acbd6-deficient zebrafish and Xenopus models effectively recapitulated many clinical phenotypes reported in patients including movement disorders, progressive neuromotor impairment, seizures, microcephaly, craniofacial dysmorphism, and midbrain defects accompanied by developmental delay with increased mortality over time. Unlike ACBD5, ACBD6 did not show a peroxisomal localisation and ACBD6-deficiency was not associated with altered peroxisomal parameters in patient fibroblasts. Significant differences in YnMyr-labelling were observed for 68 co- and 18 post-translationally N-myristoylated proteins in patient-derived fibroblasts. N-Myristoylation was similarly affected in acbd6-deficient zebrafish and Xenopus tropicalis models, including Fus, Marcks, and Chchd-related proteins implicated in neurological diseases. The present study provides evidence that bi-allelic pathogenic variants in ACBD6 lead to a distinct neurodevelopmental syndrome accompanied by complex and progressive cognitive and movement disorders.

19.
BMC Geriatr ; 23(1): 623, 2023 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-37794341

RESUMO

BACKGROUND: Falls are the third-leading cause of disability among the elderly population worldwide. It is multifactorial, and the occurrence of falls depends on different factors, which can be different from context to context, and individual to individual. Therefore, regular assessment of fall risk factors is required to develop a strategy for fall prevention. The study aimed to identify fall-related risk factors in Pakistani healthy older adults at risk of developing physical disabilities. It also aimed to create a risk-predictive model for fall occurrence, offering evidence for preventive strategies. METHODS: Data were collected from 140 Muslim older adults from two residential areas of Peshawar, Khyber Pakhtunkhwa, from July 2022 to August 25, 2022, after obtaining permission from the Zhengzhou University Ethical Review Board (ZZUIRB #202,254), and the District Health Department Office (DHO #14,207). Participants were informed, and consent was obtained before data collection. Data were collected using the Time Up and Go Test (TUGT) checklist, the Cognitive Screening Scores (CS-10) checklist, interviews regarding the prayer practice, fall history in the last six months, visual equity questions, and demographic variables. RESULTS: Factors associated with falls were; age, gender, education, cognitive status, poor walking speed, lack of physical activity, poor vision, and history of falls in the last six months, with a significant P value of (P. < 0.05) in the Pearson correlation coefficient test. Poor cognition, low visual equity, poor walking speed, and lack of exercise increase the risk of falling in the future, with a prediction value of (P < 0.005) in Omnibus, Lemeshow score of (0.77). CONCLUSION: Hence, our study provides a road map for future risk assessment of falls by adding the four mentioned risk factors in the proposed model to facilitate timely action to prevent fall-related infirmities in Pakistani healthy older adults.


Assuntos
Vida Independente , Islamismo , Humanos , Idoso , Paquistão/epidemiologia , Equilíbrio Postural , Estudos de Tempo e Movimento , Fatores de Risco , Medição de Risco
20.
Molecules ; 28(19)2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37836692

RESUMO

Inflammatory bowel disease (IBD) is a persistent, lifelong inflammation of the digestive system. Dextran sulfate sodium is commonly used to induce colitis in experimental animal models, which causes epithelial damage, intestinal inflammation, mucin depletion, and dysbiosis of the gut microbiota. Various prebiotics, polysaccharides, and polypeptides are used for IBD treatment. In this study, we used a murine model utilizing BALB/c mice, with 10 mice per group, to investigate the treatment effect of sea conch peptide hydrolysate (CPH) on DSS-induced colitis mice. Colitis was induced through the administration of 2.5% DSS in drinking water over a seven-days period. Furthermore, on the eighth day of the experiment, sea conch peptide hydrolysate (CPH) at low (100 mg/kg), medium (200 mg/kg), and high (400 mg/kg) doses, which were continued for 14 days, were assessed for medicinal purposes in DSS-induced colitis mice. Our results showed that CPH treatment significantly alleviated the severity and symptoms of colitis. The epithelial integrity and histological damage were improved. Intestinal inflammation and inflammatory cell infiltration were improved. Furthermore, the expression of pro-inflammatory cytokines was reduced, and intestinal barrier integrity was restored by elevating the tight junction proteins. Moreover, 16s RNA sequencing revealed dysbiosis of the gut microbiota was observed upon DSS treatment, which was reinstated after CPH treatment. An increased level of Firmicutes and Lactobacillus was observed in the treatment groups. Finally, our results suggest that CPH would be recommended as a functional food source and also have the potential to be used as a medicinal product for different gastrointestinal disorders.


Assuntos
Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Camundongos , Animais , Disbiose/induzido quimicamente , Disbiose/tratamento farmacológico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Citocinas/metabolismo , Inflamação/patologia , Sulfato de Dextrana/efeitos adversos , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Colo/metabolismo
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