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Histological Alterations of Cervical Cancer Following Zanthoxylum acanthopodium DC Therapy in Relation to E7, pRb, EGFR and p16 Expression

Pak J Biol Sci. 2024 Nov;27(12):602-612. doi: 10.3923/pjbs.2024.602.612.

ABSTRACT

&lt;b&gt;Background and Objective:&lt;/b&gt; Cervical cancer is the second most common cancer in Indonesia, where traditional herbal treatments like &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt; (andaliman) are culturally used. Investigating protein biomarkers such as E7, pRb, EGFR and p16 can help assess the efficacy of these treatments. &lt;b&gt;Materials and Methods:&lt;/b&gt; There were 5 groups in this study: 2 control groups (C- and C+) and 3 treatment groups (each receiving one of three doses). Oral administration of andaliman was performed for 30 days in cancer model rats, after which the cervix was dissected, cervical tissue was taken and immunohistochemistry repair was performed. Statistical analysis was performed using the Kruskal-Wallis test with a p<0.05. &lt;b&gt;Results:&lt;/b&gt; As &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt; DC dose rose, cervical tissue E7, EGFR and p16 expression decreased. However, greater doses of this plant increased cervical tissue pRb protein. Cervical cancer histology exhibited increased nuclear size, irregular cellular structure, atypical cell shape, higher nuclear-cytoplasmic ratio and various nuclear shape variants. This herb induced tissue to show well-organized non-hyperchromatic cells that resembled normal clusters. &lt;b&gt;Conclusion:&lt;/b&gt; &lt;i&gt;Zanthoxylum acanthopodium&lt;/i&gt; DC improved cervical tissue and balanced cervical cancer biomarker proteins such E7, EGFR, pRB and p16.

PMID:39731430 | DOI:10.3923/pjbs.2024.602.612

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Enhancement of Caffeine Concentration in Todolo Coffee Callus Cultures with L-Methionine and UV-Vis Spectrophotometry

Pak J Biol Sci. 2024 Nov;27(12):567-576. doi: 10.3923/pjbs.2024.567.576.

ABSTRACT

&lt;b&gt;Background and Objective:&lt;/b&gt; Todolo coffee (&lt;i&gt;Coffea arabica&lt;/i&gt; L. var. typica) is the oldest commercially grown coffee in the Toraja region of South Sulawesi and is currently at risk of extinction. This study aims to induce callus from leaf explants of Todolo arabica coffee and improve the levels of caffeine compounds in Todolo coffee with the additional precursor L-methionine as elicitor. &lt;b&gt;Materials and Methods:&lt;/b&gt; This research was conducted at the Tissue Culture Laboratory, Faculty of Mathematics and Natural Sciences, Hasanuddin University. This experimental study used a Complete Randomized Design (CRD) approach. The five stages involved callus induction, elicitation with L-methionine precursor, caffeine extraction, qualitative testing using the Parry Method and quantitative analysis via UV-Vis spectrophotometry. Tools and materials were sterilized using autoclaving and media preparation followed standard procedures with varying L-methionine concentrations. Callus induction from sterilized leaf explants was done under aseptic conditions, followed by L-methionine treatment and caffeine content extraction. Caffeine was analyzed using UV-Vis spectrophotometry at 272 nm and statistical analysis was conducted using ANOVA and DMRT at a 5% significance level. &lt;b&gt;Results:&lt;/b&gt; The friable callus structure has a shiny and wavy appearance and is more easily detached, which is highly correlated with the speed of callus growth. The callus on the treatment medium is slightly yellowish-white to somewhat brownish, indicating the production of secondary metabolites. The best concentration of L-methionine treatment was 25 mg/L with a percentage of caffeine content of 0.0078%. &lt;b&gt;Conclusion:&lt;/b&gt; Results concluded that the addition of L-methionine has a significant effect on the percentage of caffeine production.

PMID:39731426 | DOI:10.3923/pjbs.2024.567.576

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UPLC-Q-TOF-MS With Chemometrics Approach Analysis of Nonvolatile Compounds for Medicinal Citrus reticulata With Cultivar and Areas Variations

Phytochem Anal. 2024 Dec 28. doi: 10.1002/pca.3496. Online ahead of print.

ABSTRACT

INTRODUCTION: Citri Reticulatae Pericarpium (CRP), also known as Chenpi in Chinese, is the dry mature peel of Citrus reticulata Blanco or its cultivated varieties. CRP as the health-care food and dietary supplement has been widely used in various diseases. The quality of CRP can be affected by various factors, which are closely related to the metabolite composition of CRP.

OBJECTIVES: The objective of this study is to conduct a comprehensive comparative analysis on the chemical profiling of 51 C. reticulata samples of eight medicinal varieties, grown in different areas, and provide a methodological reference for the study of pharmacodynamic material bases and quality control of C. reticulata.

METHODOLOGY: Initially, a comprehensive characterization was performed using quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), and a heatmap visualization was employed for clarifying the distribution of the annotated active ingredients. Furthermore, obtained chemical profiles data were employed in multivariate statistical methods, comprising principal component analysis (PCA), and orthogonal partial least-squares-discrimination analysis (OPLS-DA).

RESULTS: A total of 42 chemical components were annotated in positive ion mode. The relative contents were evident differences in the active ingredients of medicinal varieties of C. reticulata; mostly, polymethoxy flavones (PMFs) in C. reticulata “Dahongpao” were more abundant; among them, nobiletin and tangeretin are the main active ingredients in CRP. In addition, the relative contents of chemical constituents of C. reticulata “Dahongpao” and C. reticulata “Unshiu” from different areas were less variable. Compared with production origins, the varieties of C. reticulata had a greater impact on quality.

CONCLUSION: This work obtains a better understanding of the chemical profiles of medicinal varieties of C. reticulata, facilitated the reasonable applicability and quality control of medicinal varieties of C. reticulata.

PMID:39731403 | DOI:10.1002/pca.3496

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Evaluation of bone loss in implants adjacent to a tooth or edentulous area in peri-implantitis and control murine models

J Oral Implantol. 2024 Dec 28. doi: 10.1563/aaid-joi-D-24-00100. Online ahead of print.

ABSTRACT

Peri-implantitis (PI) is an inflammatory disease that affects supportive tissues around dental implants, and its progression eventually leads to bone loss and implant failure. However, PI effects may be different based on the presence or absence of adjacent teeth.

OBJECTIVE: To investigate the differences in bone loss and inflammation between implants placed adjacent to a tooth or edentulous area in a ligature-induced PI model.

MATERIALS AND METHODS: Three-week-old C57BL/6J male mice underwent maxillary first (AT; n=12) or first and second (AE; n=8) left molar extractions. In both groups, implants were placed in the first molar region eight weeks after tooth extraction. Each group was further divided into control (C) or ligature (PI) four weeks after osseointegration. The mice were euthanized 12-14 days after ligature placement. The samples were analyzed using micro-computed tomography and histology. Statistical analysis was performed using analysis of variance and Tukey’s multiple comparison test (p<0.05).

RESULTS: Radiographic linear analysis revealed no statistically significant differences in bone levels between the C and PI groups. Linear bone loss was significantly greater in the PI group than in the C group. Volumetric analysis yielded similar results. Histologically, hematoxylin and eosin staining revealed no notable differences between the C and PI groups. The PI group showed increased levels of inflammatory infiltrates and bone resorption. Qualitative assessment of collagen through picrosirius red staining demonstrated increased collagen disorganization in the PI group compared with that in the C group. No notable differences were observed between the AT and AE groups.

CONCLUSION: The presence or absence of an adjacent tooth does not influence PI-induced soft and hard tissue alterations.

PMID:39731390 | DOI:10.1563/aaid-joi-D-24-00100

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The relationship between neuropsychological indicators and neuroimaging changes according to MRI morphometry in patients with Alzheimer’s disease and glaucoma

Zh Nevrol Psikhiatr Im S S Korsakova. 2024;124(12):142-152. doi: 10.17116/jnevro2024124121142.

ABSTRACT

OBJECTIVE: Study of neuroimaging changes according to MRI morphometry and their comparison with the structure and severity of cognitive impairment (CI) in patients with Alzheimer’s disease (AD) and primary open-angle glaucoma (POAG).

MATERIAL AND METHODS: The study involved 90 patients who were divided into two equal groups of 45 people and who early had diagnosis of AD (group 1; median age – 71 [66; 77] years) and POAG (group 2; median age – 68 [64; 77] years). 71] years). All patients underwent assessment of their neurological status, neuropsychological testing, structural MRI of the brain, followed by morphometric data processing. For the purpose of comparative assessment of the obtained MRI morphometry indicators, a group of healthy individuals was taken – group 3 (n=10).

RESULTS: In patients with AD, severe cognitive impairment (CI) was detected, and in patients with POAG, pre-dementia CI with a similar neurodegenerative nature was identified. According to MRI morphometry, in the group of patients with AD compared with POAG, there was a decrease in the volumes of gray matter of the brain, hippocampus, right thalamus, amygdala, entorhinal cortex, right cingulate gyrus, fusiform gyrus, as well as thicknesses: entorhinal cortex, cingulate gyrus and fusiform gyrus (p<0.05). When comparing volumes according to MRI morphometry with healthy individuals, patients with AD revealed a statistically significant decrease in all studied neuroimaging indicators, and when comparing thicknesses: left entorhinal cortex, fusiform gyrus; while in POAG only a decrease in the volumes of gray matter of the brain, thalamus, and right medial orbitofrontal cortex was noted.

CONCLUSION: POAG can be considered not only as an independent disease, but also as a predictor of the development of AD, therefore, the statistically significant differences we obtained between the AD group and POAG according to MRI morphometry may reflect the dynamics of the neurodegenerative process and depend on the severity of CI. In this connection, MRI morphometry can be considered not only as a method of early diagnosis, but also as an assessment of disease progression. In this case, it is important to determine not only the thicknesses, but also the volumes of brain structures according to MRI morphometry data.

PMID:39731384 | DOI:10.17116/jnevro2024124121142

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Comprehensive rehabilitation of spinal trauma patients with extended involvement of nursing staff and neurometabolic therapy

Zh Nevrol Psikhiatr Im S S Korsakova. 2024;124(12):93-98. doi: 10.17116/jnevro202412412193.

ABSTRACT

OBJECTIVE: Analysis of the effectiveness of the use of the drug Cytoflavin and the organization of the activities of nursing staff, within the framework of nursing care, in the complex therapy of patients with spinal cord injury (PSMT).

MATERIAL AND METHODS: Material and methods. 40 patients with PSMT due to a gunshot wound were examined, who were divided into two equal groups depending on the type of therapy performed: group 1 patients received the full volume of stage I medical rehabilitation (with additional use of neurodevelopmental techniques under the supervision of a Bobata department nurse) and standard drug therapy, including a course of intravenous Cytoflavin infusions followed by tablet form; group 2 patients received the full volume of stage I medical rehabilitation and standard drug therapy, but did not receive Cytoflavin. The examination included an assessment of neurological deficits on the ASIA scale and a summary assessment of sensory and motor disorders.

RESULTS: Patients in group 1 showed a greater increase in muscle strength compared to group 2. The Iu of the total muscle strength score in group 1 patients increased after treatment from 70.6±14.3 to 84.2±11.1 points, which turned out to be statistically significantly higher than in group 2 (75±7.6 and 76.5±8.5 points, respectively, p<0.05). The probability of a change in the severity of neurological disorders from more severe (type B or C) to milder (type D or E) was 4.6 times higher in patients of group 1 (OR 4.64; p<0.001).

CONCLUSION: The use of the drug Cytoflavin and classes using the Bobata method with the participation of a nurse of the department significantly increases the effectiveness of therapeutic measures in patients with PSMT.

PMID:39731377 | DOI:10.17116/jnevro202412412193

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The effectiveness of rehabilitation measures using the drug Cortexin in children with neuropsychiatric pathology

Zh Nevrol Psikhiatr Im S S Korsakova. 2024;124(12):86-92. doi: 10.17116/jnevro202412412186.

ABSTRACT

OBJECTIVE: To evaluate the effectiveness of complex rehabilitation measures using the drug Cortexin in children with neuropsychiatric pathology during a one-year follow-up.

MATERIAL AND METHODS: A promising dynamic examination and treatment of 323 children with neuropsychiatric pathology from the age of 7 days to 1 year, age 3.2±1.7 months, divided into 2 groups: the 1st group included 117 children with acute hypoxic neuropsychiatric pathology; the 2nd consisted of 98 children with chronic hypoxic neuropsychiatric pathology. Patients of both groups were randomized into 2 subgroups: patients of subgroups 1A and 2A received 2 courses of Cortexin administration with an interval of 3 months. All patients received treatment in accordance with clinical guidelines. Clinical examination and electroencephalographic mapping were used to assess the effectiveness of therapy.

RESULTS: All the examined patients showed signs of myotonic syndrome, a short-term delay in the reduction of unconditional motor automatism, delayed formation of age-related physiological motor reflexes (installation chain reactions, visual-motor interactions, manual activity, balance and walking functions). According to neurosonography, parenchymal and ventricular hematomas and signs of hydrocephalus were detected in patients. In children of subgroups 1A and 2A, the frequency and severity of symptoms after therapy differed statistically significantly from those in patients of groups 1B and 2B. Against the background of Cortexin use, 73.4% of the examined subgroups 1A and 71.3% – 1B showed an increase in bioelectric activity in the range of 10-12 Hz, an increase in signal amplitude.

CONCLUSIONS: Acute hypoxic-ischemic damage to the central nervous system determines the predominance of myotonic syndrome, and chronic hypertension-hydrocephalus syndrome. Conducting two treatment courses with the inclusion of the drug Cortexin leads to a significant reduction in the frequency and severity of manifestations of myotonic and hypertensive-hydrocephalic syndromes in children with both acute and chronic hypoxic-ischemic central nervous system damage.

PMID:39731376 | DOI:10.17116/jnevro202412412186

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Safety and efficacy of Relatox in comparison with Dysport in the treatment of focal spasticity of the upper limb in patients after stroke and traumatic brain injury (results of a prospective simple blind randomized comparative study in parallel groups)

Zh Nevrol Psikhiatr Im S S Korsakova. 2024;124(12):79-85. doi: 10.17116/jnevro202412412179.

ABSTRACT

OBJECTIVE: Evaluation of the safety and effectiveness of Relatox, botulinum toxin type A in patients with focal spasticity (FS) of the upper limb as a result of a cerebrovascular accident (CVA) or traumatic brain injury (TBI).

MATERIAL AND METHODS: A multicenter, prospective, single-blinded, randomized, comparative clinical study included 210 patients of both sexes aged 18-75 years after moderate to severe TBI and CVA in seven sites in the Russian Federation. The patients were randomized into two groups. Group 1 patients (n=105) with focal spasticity of the upper limb received Relatox injections into the muscles of the target pathological patterns (flexion of the elbow, hand, or fingers); Group 2 patients (n=105) received Dysport injections (reference agent). The drugs were injected with electromyographic (EMG) or ultrasound (US) control at a dose of no more than 400 Units of Relatox or 1000 Units of Dysport. Botulinum therapy was administered to patients for the first time or repeatedly, but not earlier than 3 months after CVA or TBI and 3 months (12 weeks) after the previous injection. At 4 and 12 weeks, spasticity was assessed using the Modified Ashworth Scale (MAS) for the muscles of the target spasticity pattern of the upper limb, the severity of disability was used to assess the Disability Assessment Scale (DAS), the severity of pain was evaluated using to the Numerical Pain Rating Scale (NPRS), and the satisfaction with treatment was measured by the Patient Global Impression of Improvement (PGI-I). The rate of adverse events (AEs) was reported.

RESULTS: A decrease in spasticity (decrease in MAS values) was shown in both groups without statistically significant intergroup differences at 4 weeks after injection for the muscles of the leading spasticity pattern of the upper limb (efficacy was assessed jointly for all target patterns) compared to the total score at the screening visit. The effect persisted for 12 weeks (more pronounced in the Relatox group). A significant decrease in pain severity according to the NPRS scale without significant intergroup differences was reported in both groups (slightly greater in Relatox group patients). The decrease in the mean DAS score with a statistically significant intergroup difference in hygiene, dressing, and overall well-being according to the PGI-I overall improvement scale was also greater in patients who received Relatox. Few local and systemic AEs were reported in both groups, with no intergroup differences. There were no significant deviations in laboratory parameters.

CONCLUSION: The results indicate the safety, good tolerability, and efficacy of Relatox in patients with focal spasticity of the upper limb after focal brain damage due to CVA or TBI, comparable and even slightly longer in duration than those of Dysport, which supports its widespread use in the rehabilitation.

PMID:39731375 | DOI:10.17116/jnevro202412412179

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Therapeutic targets of adolescent depression with attenuated symptoms of schizophrenia

Zh Nevrol Psikhiatr Im S S Korsakova. 2024;124(12):69-74. doi: 10.17116/jnevro202412412169.

ABSTRACT

OBJECTIVE: Identification of therapeutic targets in the treatment of adolescent depression with attenuated symptoms of schizophrenia and assessment of the effectiveness of therapeutic interventions.

MATERIAL AND METHODS: One hundred and twenty-three patients (mean age 19.6±2.3 years) hospitalized in the clinic of the Mental Health Research Center for adolescent depression with non-psychotic mental disorders (ICD-10: F31, F32, F33, F34; F60; F21) were examined. Group 1 (44.7%, n=55) received only psychopharmacotherapy, Group 2 (24.4%, n=30) additionally received a course of repetitive transcranial magnetic stimulation (rTMS) therapy, Group 3 (13.0%, n=16) was administered to TMS, Group 4 (17.9%, n=22) received psychotherapy. Psychometric scales (HDRS SOPS CGI, SANS) were used. Statistical analysis was performed using Statistica 12 software.

RESULTS: The addition of additional non-drug treatment methods (brain feedback and TMS) did not lead to a reliable improvement in the results, and in some cases negative results were obtained. Psychotherapy conducted according to protocols, taking into account the clinical characteristics of patients, demonstrated a significantly higher treatment effectiveness (p<0.05).

CONCLUSION: Additional therapy targets for adolescent depression with attenuated symptoms of schizophrenia have been identified, including specific mild positive, negative symptoms, and disorganization symptoms, which, although not prominent, are fundamentally important in the effectiveness of treatment.

PMID:39731373 | DOI:10.17116/jnevro202412412169

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The predictive value of thyroid hormone sensitivity parameters for cervical lymph node metastasis in patients with differentiated thyroid cancer

Ann Med. 2025 Dec;57(1):2443564. doi: 10.1080/07853890.2024.2443564. Epub 2024 Dec 27.

ABSTRACT

OBJECTIVE: To comprehensively investigate the predictive value of thyroid hormone sensitivity parameters for cervical lymph node metastasis in patients diagnosed with differentiated thyroid cancer (DTC) undergoing total thyroidectomy and neck lymph node dissection.

METHODS: A retrospective cohort study was conducted involving patients diagnosed with DTC and evaluated for cervical lymph node metastasis. Relevant demographic, tumour, lymph node and thyroid hormone sensitivity parameter data were extracted from medical records and laboratory reports. Thyroid hormone sensitivity parameters including thyroxine (T4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroglobulin antibodies (TgAbs), thyroid peroxidase antibody, thyroid hormone receptor α and TSH receptor antibody were assessed. Statistical analyses including descriptive statistics, comparative analysis, Pearson’s correlation analysis, logistic regression analysis, receiver operating characteristic (ROC) analysis and construction of a multivariable prediction model based on machine learning using the xgbTree method were employed to evaluate the associations and predictive value of thyroid hormone sensitivity parameters for cervical lymph node metastasis.

RESULTS: The study revealed significant associations between several thyroid hormone sensitivity parameters and cervical lymph node metastasis in patients with DTC. Specifically, higher levels of T4, T3, Tg, TgAbs and TSH receptor antibody were associated with lymph node metastasis. Pearson’s correlation analysis, logistic regression analysis and ROC analysis further underscored the predictive performance of these parameters, with strong overall discriminative abilities. The machine learning-based prediction model demonstrated promising performance with a high area under the curve (AUC) of 0.979.

CONCLUSIONS: The findings provide compelling evidence for the predictive value of thyroid hormone sensitivity parameters, particularly T3, T4, Tg, TgAbs and TSH receptor antibody, in identifying and evaluating the likelihood of cervical lymph node metastasis in patients with DTC. These parameters hold potential implications for risk stratification, clinical decision-making and personalized management strategies, contributing to improved outcomes for patients at risk of lymph node metastasis.

PMID:39731362 | DOI:10.1080/07853890.2024.2443564