Intraperitoneal injection of thalidomide attenuates bone cancer pain and decreases spinal tumor necrosis factor-α expression in a mouse model

<p>Abstract</p> <p>Background</p> <p>Tumor necrosis factor α (TNF-α) may have a pivotal role in the genesis of mechanical allodynia and thermal hyperalgesia during inflammatory and neuropathic pain. Thalidomide has been shown to selectively inhibit TNF-α production. Previous studies have suggested that thalidomide exerts anti-nociceptive effects in various pain models, but its effects on bone cancer pain have not previously been studied. Therefore, in the present study, we investigated the effect of thalidomide on bone cancer-induced hyperalgesia and up-regulated expression of spinal TNF-α in a mouse model.</p> <p>Results</p> <p>Osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce ongoing bone cancer related pain behaviors. At day 5, 7, 10 and 14 after operation, the expression of TNF-α in the spinal cord was higher in tumor-bearing mice compared to the sham mice. Intraperitoneal injection of thalidomide (50 mg/kg), started at day 1 after surgery and once daily thereafter until day 7, attenuated bone cancer-evoked mechanical allodynia and thermal hyperalgesia as well as the up-regulation of TNF-α in the spinal cord.</p> <p>Conclusions</p> <p>These results suggest that thalidomide can efficiently alleviate bone cancer pain and it may be a useful alternative or adjunct therapy for bone cancer pain. Our data also suggest a role of spinal TNF-α in the development of bone cancer pain.</p

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Exploring the interplay between methylation patterns and non-coding RNAs in non-small cell lung cancer: Implications for pathogenesis and therapeutic targets

Lung cancer is a global public health issue, with non-small cell lung cancer (NSCLC) accounting for 80–85 % of cases. With over two million new diagnoses annually, understanding the complex evolution of this disease is crucial. The development of lung cancer involves a complex interplay of genetic, epigenetic, and environmental factors, leading the key oncogenes and tumor suppressor genes to disorder, and activating the cancer related signaling pathway. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNA (lncRNAs), and circular RNA (circRNAs) are unique RNA transcripts with diverse biological functions. These ncRNAs are generated through genome transcription and play essential roles in cellular processes. Epigenetic modifications such as DNA methylation, N6-methyladenosine (m6A) modification, and histone methylation have gained significant attention in NSCLC research. The complexity of the interactions among these methylation modifications and ncRNAs contribute to the precise regulation of NSCLC development. This review comprehensively summarizes the associations between ncRNAs and different methylation modifications and discusses their effects on NSCLC. By elucidating these relationships, we aim to advance our understanding of NSCLC pathogenesis and identify potential therapeutic targets for this devastating disease

Serum NCAM levels and cognitive deficits in first episode schizophrenia patients versus health controls

Background: Neural cell adhesion molecule (NCAM) is a glycoprotein and plays an important role in cell-cell adhesion, neural migration, neurite outgrowth, synaptic plasticity and brain development. We investigated the relationship between the serum NCAM concentration and cognitive deficit in first episode drug naïve schizophrenia (FES) patients. Methods: Thirty FES patients and thirty healthy controls were recruited for this study. Psychiatric symptoms were assessed by the positive and negative syndrome scale (PANSS). Cognitive functions were assessed by measurement and treatment research to improve cognition in schizophrenia (MATRICS) and consensus cognitive battery (MCCB). Serum levels of NCAM were determined by ELISA. Results: Schizophrenia patients had decreased serum NCAM concentrations than controls (−30%, p Conclusions: There were a close relationship between the serum NCAM concentrations and cognitive deficits in FES patients. Since NCAM has an important role in neurodevelopmental processes, these results support the neurodevelopmental dysfunction hypothesis of schizophrenia and suggest that an altered NCAM may be one of the risk factors for schizophrenia including cognitive deficits

L-Matrices and solvability of linear complementarity problems by a linear program-Matrices and solvability of linear complementarity problems by a linear program

Linear complementarity problems, linear programs, 90C05, 90C33,

Prevalence of thyroid dysfunction in older Chinese patients with type 2 diabetes-A multicenter cross-sectional observational study across China.

Type 2 diabetes [T2D] and thyroid dysfunction [TD] often co-occur, have overlapping pathologies, and their risk increases with age. Since 1995, universal salt iodization has been implemented in China to prevent disorders caused by iodine deficiency. However, after two decades of implementation of universal salt iodization, the prevalence of TD in elderly Chinese patients with T2D is not well described and may have been underestimated. We conducted a questionnaire-based survey across 24 endocrinology centers in China between December 2015 and July 2016. Demographic and clinical data from 1677 patients with T2D were obtained and analyzed to examine the prevalence of TD along with T2D in these patients. We assessed TD prevalence according to the four TD subtypes [subclinical hypothyroidism, clinical hypothyroidism, subclinical hyperthyroidism, and clinical hyperthyroidism], TD history, gender, and age. The diagnosis rates were calculated for TD and also for the TD subtype. The number of patients reaching treatment goals for T2D [hemoglobin A1c <7%] and TD [normal free thyroxine and thyroid-stimulating hormone [TSH]] and the incidences of complications and comorbidities were recorded. Among the enrolled patients with T2D [N = 1677], TD was diagnosed in 23.79% [399/1677] out of which 61% (245/399) were previously diagnosed and 38.59% (154/399) were newly diagnosed cases. Subclinical hypothyroidism, clinical hypothyroidism, subclinical hyperthyroidism, and clinical hyperthyroidism were reported in 4.89%, 9.3%, 1.13%, and 3.16% of the total population, respectively. Among patients previously diagnosed with TD, the incidence in women [166/795; 20.88%] was higher than in men [79/882; 8.96%]. The treatment goals for TD and T2D were attained in 39.6% [97/245] and 34.41% [577/1677] of the cases, respectively. Diabetic complications and comorbidities were reported in 99.7% of patients, with peripheral neuropathy being the most common [43.46%] followed by cataract [24.73%]. We had found that the incidences of dyslipidemia, elevated LDL levels, and osteoporosis were significantly higher in patients with TD than those without TD. TD is underdiagnosed in elderly Chinese patients with T2D