The effect of green tea on inflammatory mediators: A systematic review and meta‐analysis of randomized clinical trials

Catechin in green tea might be able to reduce inflammatory mediators; therefore, in this study, we aimed to indicate green tea effects on inflammatory mediators such as tumor necrosis factor‐alpha (TNF‐α), C‐reactive protein (CRP), and interleukin‐6 (IL‐6). The advanced search methods of electronic databases were used to find randomized clinical trials that assessed green tea effect on inflammatory mediators among adult population. Google Scholar, PubMed/Medline, EMBASE, SCOPUS, and ISI Web of Science were searched until January 2019. Delphi checklist was used for assessing the quality of included articles. Mean changes in serum inflammatory biomarkers were calculated by subtracting endpoint values from the baseline in each study arm. Then the effect size for each selected study was estimated as the difference between mean changes in the intervention and control groups. We included 16 articles in our meta‐analysis and 17 articles in systematic review. Our results indicated that green tea could not significantly decrease serum CRP levels and significantly increased IL‐6 and significantly decreased TNF‐α levels. In conclusion, green tea might not be able to change inflammatory mediators especially in diseases with low inflammation, but scientists who want to assess green tea effect on inflammatory mediators should perform their study on patients with high inflammation. Studies exclusive on male or female and considering nutrients intake as a confounding factor are a necessity.     

Combined diffusion-weighted MRI and MR spectroscopy: Feasibility to improve the MRI capability in differentiation between benign and malignant neck lymphadenopathy

The study aims to evaluate the additional value of MRS and DWI in differentiating malignant and benign neck lymphadenopathy.Materials and methods: Thirty-three patients with enlarged neck lymph nodes of malignant suspicious underwent DWI and MRS. ADC values, presence of Cho peak and Cho/Creatine ratio of the dominant node were assessed and results were compared with histopathological results.Results: the patients were classified into benign (n = 9) and malignant (n = 24: 17 metastases and 7 lymphoma). The mean ADC values of the benign, metastasis and lymphoma patients were 1.56 ± 0.23, 1.01 ± 0.23 and 0.71 ± 0.02 × 10^?3 mm²/s respectively. It was significantly higher in benign than malignant (p < 0.0001) and in metastatic than lymphomatous (p = 0.001) as well as in well- and moderately than poorly differentiated metastatic (p = 0.01) lymph nodes. Using the receiver operating characteristic (ROC), cutoff value of 1.15 × 10^?3 mm²/s of ADC could differentiate benign from malignant nodes with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of 91.6%, 77.7%, 91.9%, 77.7%, KAPPA = 0.69 and p < 0.001 respectively.Malignant nodes showed a significant choline peak (n = 24, 100%) while benign nodes showed choline peak in only two cases (22%). Mean Cho/Cr ratio was significantly higher in malignant nodes than benign ones (2.64 ± 1.16 versus 1.09 ± 0.04) (p < 0.0001), furthermore it was significantly higher in lymphoma versus metastatic (4.3 ± 0.35 versus 1.94 ± 0.34, p < 0.001) as well as poor versus Well- to moderately differentiated metastases (2.3 ± 0.11 versus 1.69 ± 0.18, p < 0.01). The MRS sensitivity, specificity, PPV, NPV and Kappa in differentiating benign and malignant cervical lymph nodes were 100.0, 77.7, 92.3, 100.0% and 0.83 and p value = 0.001.Combination of DWI and MRS showed higher diagnostic value than DWI or MRS alone with sensitivity, specificity, PPV, NPV and Kappa of 100, 88.9, 96, 100% and 0.92 respectively (p < 0.0001).Conclusion: ADC and MRS can help in the differentiation between malignant and benign neck lymph nodes. Combination of both techniques achieved higher diagnostic performance.     

Human placenta-derived adherent cells prevent bone loss, stimulate bone formation, and suppress growth of multiple myeloma in bone

Human placenta has emerged as a valuable source of transplantable cells of mesenchymal and hematopoietic origin for multiple cytotherapeutic purposes, including enhanced engraftment of hematopoietic stem cells, modulation of inflammation, bone repair, and cancer. Placenta-derived adherent cells (PDACs) are mesenchymal-like stem cells isolated from postpartum human placenta. Multiple myeloma is closely associated with induction of bone disease and large lytic lesions, which are often not repaired and are usually the sites of relapses. We evaluated the antimyeloma therapeutic potential, in vivo survival, and trafficking of PDACs in the severe combined immunodeficiency (SCID)-rab model of medullary myeloma-associated bone loss. Intrabone injection of PDACs into nonmyelomatous and myelomatous implanted bone in SCID-rab mice promoted bone formation by stimulating endogenous osteoblastogenesis, and most PDACs disappeared from bone within 4 weeks. PDACs inhibitory effects on myeloma bone disease and tumor growth were dose-dependent and comparable with those of fetal human mesenchymal stem cells (MSCs). Intrabone, but not subcutaneous, engraftment of PDACs inhibited bone disease and tumor growth in SCID-rab mice. Intratumor injection of PDACs had no effect on subcutaneous growth of myeloma cells. A small number of intravenously injected PDACs trafficked into myelomatous bone. Myeloma cell growth rate in vitro was lower in coculture with PDACs than with MSCs from human fetal bone or myeloma patients. PDACs also promoted apoptosis in osteoclast precursors and inhibited their differentiation. This study suggests that altering the bone marrow microenvironment with PDAC cytotherapy attenuates growth of myeloma and that PDAC cytotherapy is a promising therapeutic approach for myeloma osteolysis.     

Serotonin transporter gene polymorphisms and brain function during emotional distraction from cognitive processing in posttraumatic stress disorder

Background

Serotonergic system dysfunction has been implicated in posttraumatic stress disorder (PTSD). Genetic polymorphisms associated with serotonin signaling may predict differences in brain circuitry involved in emotion processing and deficits associated with PTSD. In healthy individuals, common functional polymorphisms in the serotonin transporter gene (SLC6A4) have been shown to modulate amygdala and prefrontal cortex (PFC) activity in response to salient emotional stimuli. Similar patterns of differential neural responses to emotional stimuli have been demonstrated in PTSD but genetic factors influencing these activations have yet to be examined.

Methods

We investigated whether SLC6A4 promoter polymorphisms (5-HTTLPR, rs25531) and several downstream single nucleotide polymorphisms (SNPs) modulated activity of brain regions involved in the cognitive control of emotion in post-9/11 veterans with PTSD. We used functional MRI to examine neural activity in a PTSD group (n = 22) and a trauma-exposed control group (n = 20) in response to trauma-related images presented as task-irrelevant distractors during the active maintenance period of a delayed-response working memory task. Regions of interest were derived by contrasting activation for the most distracting and least distracting conditions across participants.

Results

In patients with PTSD, when compared to trauma-exposed controls, rs16965628 (associated with serotonin transporter gene expression) modulated task-related ventrolateral PFC activation and 5-HTTLPR tended to modulate left amygdala activation. Subsequent to combat-related trauma, these SLC6A4 polymorphisms may bias serotonin signaling and the neural circuitry mediating cognitive control of emotion in patients with PTSD.

Conclusions

The SLC6A4 SNP rs16965628 and 5-HTTLPR are associated with a bias in neural responses to traumatic reminders and cognitive control of emotions in patients with PTSD. Functional MRI may help identify intermediate phenotypes and dimensions of PTSD that clarify the functional link between genes and disease phenotype, and also highlight features of PTSD that show more proximal influence of susceptibility genes compared to current clinical categorizations.

     

Differential patterns of initial and sustained responses in amygdala and cortical regions to emotional stimuli in schizophrenia patients and healthy participants

Background

We sought to investigate the altered brain responses to emotional stimuli in patients with schizophrenia.

Methods

We analyzed data from 14 patients with schizophrenia and 14 healthy controls who performed an emotional face matching task. We evaluated brain activity and connectivity in the amygdala and cortical regions during the initial (first 21 seconds of each stimulation block) and sustained (last 21 seconds) stages of an emotional processing task, and we determined changes in amygdala activity across the emotional processing task.

Results

The patients with schizophrenia showed similar amygdala activation to the controls during the initial stage of processing, but their activation decreased during the sustained stage. The controls showed increasing amygdala activity across the emotional blocks, whereas activity progressively decreased in the schizophrenia group. The patients with schizophrenia showed increased cortical activity and interconnectivity in the medial frontal and inferior parietal cortex in the initial stage of emotional processing. There was increased activity in the superior temporal cortex and greater connectivity with the inferior parietal cortex in the sustained stage. Performance accuracy was lower in the schizophrenia group in the first part of the block, while their reaction time was longer in the latter part of the block.

Limitations

It was not possible to specify the moment at which the switch in amygdala response occurred.

Conclusion

Our findings suggest that patients with schizophrenia have an initial automatic emotional response but that they need to switch to a compensatory cognitive strategy to solve the task.