International journal of physiology, pathophysiology and pharmacology最新文献

Background: Cell transplantation is a promising treatment for the patients with end-stage liver diseases. Stem cells derived hepatocyte-like cells (HLCs) attenuated liver injury upon transplantation in animal models for liver fibrosis. However, only a small portion of the transplanted cells propagated in the recipient liver.

Aim: We hypothesized that the efficiency of cell therapy could be improved by transplanting amniotic mesenchymal stem cells (AMSCs) derived HLCs along with human umbilical vein endothelial cells (HUVECs) and undifferentiated AMSCs.

Methods: Briefly, we used a two-step protocol to generate induced HLCs. We confirmed organoids formation of HLCs in 3D collagen scaffolds with HUVECs and AMSCs. To determine whether the HLCs can migrate into the liver tissue and perform in vivo function, we transplanted the cells to mice with liver fibrosis.

Results: Co-culture of HLCs with HUVECs and AMSCs demonstrated improved function of HLCs within the organoids. Furthermore, transplantation using non-homogeneous cells, i.e. HLCs mixed with HUVECs and AMSCs, exhibited better graft survival in the host animals with liver fibrosis. Our experiment results suggested that compared to mock transplantation or HLCs transplantation groups, liver fibrosis was reduced significantly in mixed-cell groups. The AST levels in the plasma of transplanted mice were markedly decreased only in the mixed-cell transplantation group. The engraftment of HLCs in mice liver was better in mixed-cell transplantation group, compared with HLCs-only transplantation group.

Conclusions: The HLCs attenuated liver fibrosis more efficiently when transplanted along with HUVECs and AMSCs, and this suggested that we could improve the efficiency of cell therapy by transplanting functional cells partially along with stromal cells.

Background: Identification of factors affecting prognosis in chronic lymphocytic leukemia (CLL) is important for risk stratification of patients.

Methods: In the present study, CD49d expression was analyzed by multi-color flow cytometry in 98 newly diagnosed and untreated CLL patients at the hematopathology ward. The patients were divided into two subgroups according to CD49d expression (30% cut off) and the association of this marker with the patients' clinicopathological properties were evaluated.

Results: In this study, CD49d expression exhibited significant association with the Rai stage of the disease (P<0.0001), CD38 status (P<0.0001), hemoglobin level (P=0.0006), and platelet count (P=0.0016). The CD49d-positive patients presented in higher stages in comparison with CD49d-negative patients. Although only 1% of the CD49d-negative patients were CD38-positive, this proportion for CD49d-positive group was 69%. However, no significant correlation was observed between CD49d expression and patients' age (P=0.2031), gender (P=0.8119), and absolute lymphocytes count (P=0.1073).

Conclusion: Therefore, CD49d is a grateful biomarker with high association with clinicopathological parameters in CLL patients.

Cellular structures that perform essential homeostatic functions include tight junctions, gap junctions, desmosomes and adherens junctions. The aqueous humor, produced by the ciliary body, passes into the anterior chamber of the eye and is filtered by the trabecular meshwork (TM), a tiny tissue found in the angle of the eye. This tissue, along with Schlemm's canal (SC) inner wall cells, is thought to control intraocular pressure (IOP) homeostasis for normal, optimal vision. The actin cytoskeleton of the tissue plays a regulatory role in maintaining IOP. One of the key risk factors for primary open angle glaucoma is persistent elevation of IOP, which compromises the optic nerve. The ZO-1 (Zonula Occludens-1), extracellular matrix protein integrins, and gap junction protein connexin43 (Cx43) are widely expressed in many different cell populations. Here, we investigated the localization and interactions of ZO-1, α3 integrin, β1 integrin, and Cx43 in cultured porcine TM and SC cells using RT-PCR, western immunoblotting and immunofluorescence labeling with confocal microscopy, along with co-immunoprecipitation. ZO-1 partially co-localized with α3 integrin, but not with β1 integrin, and co-immunoprecipitated with Cx43, as well as with α3 integrin. The association of ZO-1 with α3 integrin and Cx43 suggests that these proteins may form a multiple protein complex in porcine TM and SC cells. Since integrins interact with the actin cytoskeleton via scaffolding proteins, these results implicate junctional and scaffolding protein ZO-1 as a potential control point in regulation of IOP to normal levels for glaucoma therapy.

Human trabecular meshwork (TM) cells play pivotal roles in maintaining homeostasis of intraocular pressure via regulation of aqueous humor outflow. These cells are capable of phagocytosis, which is considered to be essential for their regulatory function. In addition, there is a strong expression of the gap junction protein connexin43 (Cx43) in the TM. Here, we investigated functional relationships between phagocytosis activity of TM cells and their expression of Cx43. Phagocytosis was measured by showing the ability of TM cells to engulf inert fluorescent particles consisting of pHrodo. We found that internalized pHrodo was partially co-localized with Cx43 and that the phagocytic activity was dramatically reduced after knockdown of Cx43 using lentiviral Cx43 shRNA. These results suggest that Cx43 is involved in the regulation of phagocytosis by TM cells.

Background and objective: Pectoral Nerve (PECs) block is a fascial plane block first described by Blanco et al. for postoperative analgesia in breast surgery. The procedure is now widely used, and several small clinical trials have been published and reported favorably on the analgesic efficacy of PECs block. In this systematic review and meta-analysis, we will summarize the current evidence on the efficacy of PECs block.

Methods: We identified and analyzed 19 randomized control trials from PubMed, Central, EMBASE, CINAHL, Web of Science citation index, US clinical trials register and Google Scholar. The primary outcome was 24-hour opioid requirement, and secondary outcomes included pain scores, postoperative nausea and vomiting and other complications.

Results: Compared to systemic analgesia, PECs block was associated with reduced 24 hours opioid requirement [mean difference (MD) = -10.66 mg], lower pain score [9-12 hours postoperatively: MD = -1.18; 24 hours postoperatively: MD = -0.79] and less frequent PONV [risk ratio (RR) = 0.37, numbers needed to treat (NNT) = 5]. While the failure rate of PECs block was not well defined, several studies reported significant intraoperative opioid requirement despite PECs block. Lastly, trial sequential analysis indicated that no more clinical trials are needed to demonstrate the opioid sparing effect of PECs block.

Conclusion: When compared to general anesthesia with systemic opioids, PECs block was associated with significantly better perioperative pain control. There are currently insufficient data on the complication and failure rate of PECs block in clinical practice.

Membrane fusion is a universal event in all living organism. It is at the heart of intracellular organelle biogenesis and membrane traffic processes such as endocytosis and exocytosis, and is also used by enveloped viruses to enter hosting cells. Regarding the cellular mechanisms underlying membrane fusion, pioneering studies by Randy Schekman, James Rothman, Thomas C. Südhof and their colleagues have demonstrated the function of specific proteins and protein-protein interactions as essential fusogenic factor to initiate membrane fusion. Since then, function of lipids and protein-lipid interaction has also been identified as important players in membrane fusion. Based on that NSF (NEM-sensitive factor where NEM stands for N-ethyl-maleimide) and acyl-CoA are required for the membrane fusion of transporting vesicles with Golgi cisternae, it is further suggested that the transfer of the acyl chain to a molecule(s) is essential for membrane fusion. Among the previously identified fusogens, phosphatidic acid (PA) is found as an acyl chain recipient. Functionally, acylation of PA is required for tethering the membranes of Rab5a vesicles and early endosomes together during membrane fusion. As certain threshold of proximity between the donor and acceptor membrane is required to initiate membrane fusion, fusogenic factors beyond protein-protein and protein-lipid interaction need to be identified.

There is strong evidence for the positive physical health outcomes of physical conditioning (athletic training. But there is a dearth of data on the impact of exercise on cognition, particularly in the adolescent age group. Further, most of the studies done on this topic are mainly acute in nature, and few that have seen long term effect of exercise have very rarely used objective measures such as event-related potentials. Hence, the present study was conceived to compare cognition in athletes (individual who have undergone long term physical activity) and non-athletes. We designed a cross-sectional comparative study involving apparently healthy volunteer boys in the age group of 10-19 years-non-athletes (n = 30) and athletes (n = 30). Paper pencil tests such as letter cancellation test, auditory and visual recognition reaction time, trail making test (A and B) were recorded along with auditory event-related potentials (N100, P200, N200, and P300). Data were analyzed using an unpaired t-test and Mann-Whitney U test according to the data distribution. Athletes completed letter cancellation task and trail making test faster than non-athletes. Athletes visual and auditory reaction time were lesser. Athletes had reduced latency and higher amplitude of auditory event-related potentials (N100, P200, N200, and P300) as compared to non-athletes. Hence, we conclude that athletic level physical training has a beneficial role in the executive cognitive domain among adolescents.

Background: Disseminated cryptococcosis is less common in individuals with normal immune function. Most cases occur in HIV-infected people. Usually it affects the lungs, followed by the central nervous system (CNS), skin and bone marrow, but rarely to the lymph nodes and chest wall.

Case presentation: This article reports a case of cryptococcal infection diagnosed as "lymphoma?" in a local hospital. It was characterized by chronic fever, weight loss, neck, axillary and inguinal lymph nodes enlargement, mediastinal and parabronchial lymphadenopathy, multiple nodular high-density images of both lungs, multi-serosal effusion, liver enlargement and other presentations.

Conclusions: Disseminated cryptococcosis can occur in immunocompromised children without HIV infection. This case of multiple and mediastinal lymphadenopathy, easily misdiagnosed as "lymphoma", requires high clinical suspicion and early initiation of treatment to effectively identify and treat patients.

Background: Studies reported that evaluating the interleukin serum level of MS and NMO patients is helpful for differentiating these two diseases from each other. This study aimed to compare the level of IL-6 and IL-17 in MS and NMO patients and healthy subjects.

Methods: This study is a case control study that evaluated the serum level of IL-6 and IL-17 in MS and NMO patients in comparison to controls in patients who referred to Kashani hospital clinics. The level of serum IL-6 and IL-17 were measured by ELISA test in all patients. Participants were divided in to three groups include MS patients, NMO patients and controls and the level of IL-6 and IL-17 were compared in this three groups.

Results: Mean of serum level of IL-6 in the NMO group was significantly lower than MS and healthy subject (P=0.02 for NMO and MS, P=0.001 for NMO and healthy subjects) but there was no significant difference between MS and healthy subjects (P=0.09). The mean of serum level of IL-17 in the MS and NMO were significantly higher than healthy subjects (P<0.001 for both). Also the mean of serum level of IL-17 in the MS was significantly higher than NMO (P=0.01). A positive significant correlation between age and serum level of IL-6 in all subjects (r=0.23, P=0.01). There was a positive significant correlation between age and serum level of IL-17 in MS and NMO patients (r=0.28, P=0.012).

Conclusion: Using IL-17 and IL-6 were inflammatory markers to diagnosis of NMO, MS and healthy subjects.

CD200 and its receptor, CD200R, constitutes an endogenous inhibitory signaling, and is being increasingly recognized in studies of various central nervous system (CNS) disorders. Emerging data have demonstrated that neuronal CD200 binds to CD200R to modulate immune responses to pathogenic stimuli. However, on which component of the immune response that CD200-CD200R signaling acts is not well understood. In this review, we focused on cellular expression of the signaling, the effects on immune cell activation, and the function in pathological procedures of neurodegenerative diseases, in both clinical and experimental disease models. Essential functions of CD200-CD200R interaction and the treatment relevance have been elaborated. Immune responses to diseases under the control of CD200-CD200R axis were also discussed in the review.