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Hypothesis Open Access
Subramanya Adiga
Published online May 29, 2024
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Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2023.00020
Abstract
Following complete peripheral nerve injury, collateral sprouting (CS) by adjacent nerves causes concentric shrinkage of the insensate area. Such take-over of insensate territory [...] Read more.

Following complete peripheral nerve injury, collateral sprouting (CS) by adjacent nerves causes concentric shrinkage of the insensate area. Such take-over of insensate territory is unknown in proximal lesions such as stroke, spinal cord injury, and cauda equina syndrome, as peripheral nerves supplying insensate territories still maintain continuity from the cell body in the dorsal root ganglion (DRG) to the skin innervation territory. This preserved distal continuity opposes territory take-over by the expansion of adjacent sensate territories; sectioning peripheral nerves in insensate territories distal to DRGs disconnects nerve cell bodies from their skin territory, thus facilitating sensate territory expansion of adjacent nerves. Similar motor system applications in paralyzed territories include lower motor neurone lesioning and fasciectomies, facilitating motor territory expansion of adjacent nerves through CS. A search for evidence of previous conception of these hypotheses was conducted in the literature, using a combination of relevant terms from three categories (proximal neuraxial lesions, nerve-muscle interventions, collateral sprouting); however, this yielded no pertinent results, suggesting that these concepts are novel. Observations from the literature on peripheral nerve injury indicate a sound scientific basis for these hypotheses. Therefore, the suggested “weeding” interventions are likely to succeed in minimizing neurological deficits and improving patients’ quality of life. Various interventions to expand sensory/motor territories are considered; these include nerve lesioning distal to DRGs and removing fascial barriers between innervated and paralyzed muscles. Experience from such interventions will help expand our understanding of the speed and extent of CS-mediated neurological recovery as well as brain’s plastic abilities in reorienting after such procedures.

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Original Article Open Access
Mathias A. Emokpae, Lawrence Ogana
Published online May 29, 2024
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Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2023.00085
Abstract
Harm caused by crude oil spillage and its associated environmental toxicants manifests slowly. This study examined the impact of crude oil environmental toxicants on neonates’ thyroid [...] Read more.

Harm caused by crude oil spillage and its associated environmental toxicants manifests slowly. This study examined the impact of crude oil environmental toxicants on neonates’ thyroid and cognitive functions in crude oil-producing communities.

The case-control study comprised 55 crude oil-exposed expectant mothers and 33 non-crude oil-exposed expectant mothers as controls. Serum Benzo Pyrene Dihydrodiol Epoxide (BPDE), triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) were assayed in expectant mothers and neonates. Intelligence quotient and APGAR scores were determined in the children using Fagan’s test of infant intelligence.

Serum TSH (p < 0.05) and BPDE (p < 0.001) were higher, while T3 and T3/T4 ratio were significantly lower (p < 0.001) in exposed pregnant women compared to the control. Cord blood TSH and T3/T4 ratio were lower (p < 0.001) while T4 and BDPE were higher (p < 0.001) in prenatally exposed neonates than prenatally non-exposed infants. Serum TSH correlated with BDPE (R2 = 0.080, p < 0.036) and APGAR score (R2 = 0.341, p < 0.012), while T3 and T4 were not associated with BDPE and APGAR score. TSH correlated with T3 (R2 = 0.0.082, p < 0.05), T3 correlated with T4 (R2 = 0.111, p < 0.013) and TSH (R2 = 0.082, p < 0.05). Exactly 54.5% (30/55) of prenatally exposed neonates had a low intelligence quotient compared to 36.4% (12/33) in prenatally non-exposed neonates.

Crude oil and associated environmental pollutants might significantly affect the thyroid function. Environmental surveillance, biomonitoring and environmental cleanup are emphasized. Future research on the mechanisms of the observed toxicological effects on thyroid hormones and targeted protection of pregnant women and their offspring is suggested.

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Commentary Open Access
Wenxue Ma, Theia Minev
Published online September 24, 2024
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Oncology Advances. doi:10.14218/OnA.2024.00020
Original Article Open Access
Mengxia Yang, Chunming Zhao, Tengfei Chen, Xiaolong Xu, Qingquan Liu
Published online August 30, 2024
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Future Integrative Medicine. doi:10.14218/FIM.2024.00030
Abstract
Shufeng Jiedu Capsules (SFJD), a traditional Chinese medicine preparation, are widely used in the clinical treatment of influenza, yet their mechanism of action remains unclear. [...] Read more.

Shufeng Jiedu Capsules (SFJD), a traditional Chinese medicine preparation, are widely used in the clinical treatment of influenza, yet their mechanism of action remains unclear. This study aimed to systematically explore the molecular mechanism of SFJD in the treatment of influenza using network pharmacology and bioinformatics techniques.

The active ingredients of SFJD were retrieved from traditional Chinese medicine databases, and their targets were identified using the Swiss Target Prediction and TCMSP databases. Influenza disease genes were obtained from the GEO, GeneCards, and DisGeNET databases, and a Venn diagram was used to identify potential targets by mapping SFJD targets to influenza disease genes. Network construction and analysis of potential therapeutic targets were performed using the STRING12.0 database and Cytoscape3.9.1 software, leading to the identification of key targets. The expression of potential therapeutic targets in tissues and cells was retrieved using the BioGPS database. Functional enrichment analysis of these targets was conducted using the DAVID database. Molecular docking was then used to assess the interactions between key targets and core active ingredients.

SFJD contains 193 active ingredients and 985 targets. There are 510 influenza disease genes, 97 of which are potential therapeutic targets for SFJD in treating influenza, with 27 key targets identified through network construction and analysis. Tissue/cell-specific analysis revealed that 39 potential therapeutic targets are highly expressed in 37 specific tissues/cells. Functional enrichment analysis highlighted pathways such as the C-type lectin receptor signaling pathway, tumor necrosis factor signaling pathway, and hypoxia-inducible factor-1 signaling pathway. Molecular docking results indicated strong interactions between the core active ingredients and the key targets.

This study systematically reveals that the mechanism of action of SFJD in treating influenza is complex, involving multiple targets and pathways related to antiviral, anti-inflammatory, and immune regulation effects. The findings provide valuable reference information for future clinical treatment and basic research on influenza.

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Review Article Open Access
Tian Xiao, Didi Chen, Li Peng, Zhuoxia Li, Wenming Pan, Yuping Dong, Jinxiang Zhang, Min Li
Published online January 2, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00375
Abstract
Fluorescence navigation is a novel technique for accurately identifying hepatocellular carcinoma (HCC) lesions during hepatectomy, enabling real-time visualization. Indocyanine [...] Read more.

Fluorescence navigation is a novel technique for accurately identifying hepatocellular carcinoma (HCC) lesions during hepatectomy, enabling real-time visualization. Indocyanine green-based fluorescence guidance has been commonly used to demarcate HCC lesion boundaries, but it cannot distinguish between benign and malignant liver tumors. This review focused on the clinical applications and limitations of indocyanine green, as well as recent advances in novel fluorescent probes for fluorescence-guided surgery of HCC. It covers traditional fluorescent imaging probes such as enzymes, reactive oxygen species, reactive sulfur species, and pH-sensitive probes, followed by an introduction to aggregation-induced emission probes. Aggregation-induced emission probes exhibit strong fluorescence, low background signals, excellent biocompatibility, and high photostability in the aggregate state, but show no fluorescence in dilute solutions. Design strategies for these probes may offer insights for developing novel fluorescent probes for the real-time identification and navigation of HCC during surgery.

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Original Article Open Access
Nadezhda Bakalenko, Daria Smirnova, Liana Gaifullina, Polina Kuchur, Daniela Ian, Mikhail Atyukov, Ju Liu, Anna Malashicheva
Published online June 30, 2024
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Gene Expression. doi:10.14218/GE.2024.00006
Abstract
Idiopathic pulmonary fibrosis is a chronic, progressive, incurable lung disease, leading to irreversible lung tissue remodeling. The Notch signaling pathway, essential for lung [...] Read more.

Idiopathic pulmonary fibrosis is a chronic, progressive, incurable lung disease, leading to irreversible lung tissue remodeling. The Notch signaling pathway, essential for lung development, has gained attention for its role in pulmonary fibrosis. While Notch1 and Notch3 have been extensively studied, the involvement of other Notch receptors, especially Notch4, remains less explored. This study aimed to evaluate the impact of Notch4 on lung fibroblast activation and its potential interaction with the transforming growth factor-beta 1 (TGFβ1) signaling.

Primary human lung fibroblasts were transduced with lentivirus containing the intracellular domain of NOTCH4 (N4ICD). Changes in gene expression in transduced cells were assessed using real-time polymerase chain reaction, immunofluorescence staining, and Western blotting. Transcriptomic analysis was also performed on N4ICD-transduced lung fibroblasts.

N4ICD overexpression significantly upregulated key fibrotic markers such as ACTA2 and COL1A1. It also induced the TGFβ1 pathway, as evidenced by SMAD2 phosphorylation and elevated TGFβ1 mRNA level. Transcriptomic analysis revealed that N4ICD-induced cells exhibited characteristics of highly invasive myofibroblasts.

This study establishes Notch4 as a novel contributor to pulmonary fibrosis, by demonstrating its ability to induce myofibroblast differentiation and interact with the TGFβ1 pathway.

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Review Article Open Access
Indre Zaparackaite, Shailinder Jit Singh, Debashish Bhattacharya, Swamy Kaki Bale, Rafael Cavalcante Correia, Partap Kumar Midha, Dhaval Govani, Ramnik Vallabh Patel
Published online September 10, 2024
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Journal of Translational Gastroenterology. doi:10.14218/JTG.2023.00092
Abstract
Based on our experimental and clinical research, the gastroschisis is formed by raised intraluminal and intraabdominal pressure in combination with potential weak points. The psycho-neuro-endocrine-target [...] Read more.

Based on our experimental and clinical research, the gastroschisis is formed by raised intraluminal and intraabdominal pressure in combination with potential weak points. The psycho-neuro-endocrine-target organ axis of young mothers, who themselves struggle to meet their macro and micronutrient requirements, places a burden on the placenta. The associated smoking, alcohol, drugs, and other toxins, leads to fetal distress. This activates the same fetal axis, with the final common pathway being activated via the sacral parasympathetic nervous system as a flight or fight response leading to colorectal secreto-motility disorder of the hindgut and small left colon leading to partial functional obstruction of hindgut. This leads to pressure build-up on the proximal colon. An intact ileocecal valve leads to blind loop obstruction, creating the force required to herniate the bowel through the defect at three key points of weakness in the abdominal wall, the most vulnerable being the right paraumbilical region. If the ileocecal valve becomes incompetent, variants of gastroschisis may occur. The fetus, particularly the peritoneum, always has a tendency to heal defects quickly, which forms secondary events in the eviscerated bowel causing the closing and closed gastroschisis with vanishing organs. Recent technological advances in preformed silastic silo innovation, prenatal diagnosis and monitoring for closing gastroschisis, perinatal management, percutaneous central long lines, and innovative minimally invasive bedside procedures, have all made significant contributions. We believe that gastroschisis is the external surgical symptom and peak of the iceberg, secondary to an underlying colorectal motility disorder, providing the force to eviscerate bowel loops through potential weak points and its subsequent sequelae.

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Review Article Open Access
Zhuoya Sun, Lupeng Qiu, Xiao Zhao, Shunchang Jiao
Published online June 25, 2024
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Oncology Advances. doi:10.14218/OnA.2023.00043
Abstract
The tumor microenvironment is a dynamic cellular landscape critical to cancer progression. Within it, tumor-infiltrating lymphocytes hold a dual role, contributing to both tumor [...] Read more.

The tumor microenvironment is a dynamic cellular landscape critical to cancer progression. Within it, tumor-infiltrating lymphocytes hold a dual role, contributing to both tumor suppression and progression. This review synthesized current knowledge on tumor-infiltrating lymphocytes, emphasizing their prognostic significance and therapeutic potential. By dissecting their interactions within the tumor microenvironment and with cancer cells, we sought to uncover the complexities of the immune response in cancer and explored the future direction of immunotherapeutic strategies.

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Original Article Open Access
Kayla Brice, Candice Arline, Luis E. Raez, Katerine Dumais, Mark Block
Published online September 25, 2024
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Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00021
Abstract
Tumor molecular analysis using next-generation sequencing (NGS) is the standard of care for guiding lung cancer treatment. Endobronchial ultrasound-guided transbronchial needle [...] Read more.

Tumor molecular analysis using next-generation sequencing (NGS) is the standard of care for guiding lung cancer treatment. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique used to sample mediastinal lymph nodes for diagnosing and staging lung cancer. This study aimed to determine if EBUS-TBNA provided adequate tissue samples for NGS.

We evaluated EBUS-TBNA samples from adult advanced non-small cell lung cancer patients who had both EBUS-TBNA and liquid biopsy samples analyzed by NGS between July 1, 2015 and June 30, 2021. Additionally, we compared the results with those from liquid biopsies performed on these patients.

Among the 44 evaluated patients, 43% were male, with a median age of 66 years at diagnosis. Seventy-five percent were smokers, 79.5% were White, 6.8% were Black, and 9.1% were Asian. EBUS-TBNA samples were sufficient for NGS in 95.5% of cases. The median turnaround time for EBUS-TBNA NGS was 38.5 days compared with eight days for NGS in liquid biopsies. Actionable genetic aberrations were detected in 71% of patients.

Our findings demonstrated that EBUS-TBNA provided sufficient tissue for identifying actionable genetic aberrations in patients with advanced non-small cell lung cancer.

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Illuminating and Instructive Clinical Case Open Access
Kai Liu, Ziyue Huang, Lijin Zhao, Haitao Zhao
Published online January 2, 2025
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Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00404
Abstract
Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) deletions are frequently identified in patients with biliary tract cancer; however, standard treatment options for this genetic [...] Read more.

Cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/2B) deletions are frequently identified in patients with biliary tract cancer; however, standard treatment options for this genetic alteration are lacking. Here, we present the case of a 64-year-old woman diagnosed with intrahepatic cholangiocarcinoma and hilar lymph node metastasis who underwent radical surgery. Postoperative pathology confirmed moderately differentiated adenocarcinoma. The tumor recurred during the second cycle of adjuvant chemotherapy following surgery, and the metastatic sites included the cranial region, right lung, and right adrenal gland. Genetic analysis revealed a CDKN2A/2B deletion, indicating palbociclib sensitivity. Subsequently, the patient received palbociclib plus lenvatinib as systemic therapy, along with stereotactic radiotherapy for the intracranial lesion. Notably, the right pulmonary metastasis significantly regressed after 12 months of treatment, with the complete disappearance of the intracranial tumor. However, the disease progressed at 32.2 months, with significant enlargement of the right adrenal gland metastasis and new metastasis in the right lung. The progression-free survival and overall survival were 32.2 months and 34.4 months, respectively. In conclusion, our case demonstrates that palbociclib plus lenvatinib is a promising chemotherapy-free second-line treatment for intrahepatic cholangiocarcinoma with a CDKN2A/2B deletion.

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