Monomorphic epitheliotropic intestinal T-cell lymphoma with bone marrow involved: A case report.

BACKGROUND: Monomorphic epithelial intestinal T-cell lymphoma (MEITL) is a rare type of peripheral T-cell lymphoma. The clinical manifestations are diarrhea, abdominal pain, perforation and an abdominal mass. CASE SUMMARY: We present a 52-year-old female patient who was diagnosed with MEITL. Further disease progression was observed after multiline chemotherapy. Eventually, the patient died of a severe infection. CONCLUSION: MEITL is a rare intestinal primary T-cell lymphoma with aggressive behavior, a high risk of severe life-threatening complications, and a poor prognosis.

Sequence determinants of human junctophilin-2 protein nuclear localization and phase separation.

Junctophilin-2 (JPH2) was conventionally considered as a structural membrane binding protein. Recently, it was shown that proteolytically truncated mouse JPH2 variants are imported into nucleus to exert alternative functions. However, the intranuclear behaviors of human JPH2 (hJPH2) and underlying molecular determinants have not been explored. Here, we demonstrate that full-length hJPH2 is imported into nucleus in human cells by two nuclear localization signals (NLSs), including a newly discovered one at the C-terminus. Importantly, unlike the JPH2 N-terminal truncation which diffuses throughout the nucleus, full-length hJPH2 forms nuclear bodies behaving like liquid-liquid phase separated droplets that are separated from chromatin. The C-terminal transmembrane domain is required for the formation of hJPH2 droplets. Oxidation mimicking substitution of residues C678 and M679 augments the formation of hJPH2 nuclear droplets, suggesting nuclear hJPH2 liquid-liquid phase separation could be modulated by oxidative stress. Mutation A405D, which introduces a negatively charged residue into an intrinsic disordered region (IDR) of hJPH2, turns liquid-like droplets into amyloid-like aggregates. Depletion of an Alanine Rich Region in the IDR recapitulates the liquid-amyloid phase transition. The MORN repeat regions of hJPH2 encodes intrinsic tendency to form amyloid-like structure. Together, these data revealed the novel intrinsic properties of hJPH2 to form nuclear liquid droplets, and identified critical functional domains encoding these properties. We propose that hJPH2 droplets could function as membrane-less organelles participating in nuclear regulatory processes.

cis-Silicon phthalocyanine conformation endows J-aggregated nanosphere with unique near-infrared absorbance and fluorescence enhancement: a tumor sensitive phototheranostic agent with deep tissue penetrating ability.

Organic phototheranostic nanomedicines with an optimized near-infrared (NIR) biological transparent window (700-900 nm) are highly desirable for the diagnosis and treatment of deep-seated tumors in clinic. As excellent organic photosensitizers for photodynamic therapy (PDT) with outstanding photo- and thermo-stability, phthalocyanines (Pcs) have been used as the building blocks of single-component nanomedicines. However, to the best of our knowledge, all the Pc-based single-component self-assemblies reported to date are of an H-aggregate nature. This results in the simultaneous self-quenching of fluorescence emission and photodynamic activity as well as greatly reduced tissue penetration due to blue-shifted absorption. In the present work, intramolecular hydrogen bonding was formed between the two long and flexible axial NH2-terminated diethylene glycol ligands of the amphiphilic SiPc molecule (SiPc-NH2) in solution, leading to the employment of a cis-conformation of this molecule according to the 1H-NMR spectroscopy result, which as a building block then further self-assembled into monodisperse nanospheres (SiPcNano) with a J-aggregation nature on the basis of electronic absorption spectroscopic results. As a result, SiPcNano exhibited significantly enhanced red-shifted absorption in the NIR range of 750-850 nm and fluorescence emission. This in combination with the increased photodynamic effect for SiPcNano triggered by the protonation of amine groups due to the acidic nature of tumors endowed effective synergistic NIR photodynamic and photothermal effects in different cancer cells and thus effective inhibition of tumor growth in A549 tumor-bearing mice on the basis of a series of in vitro and in vivo evaluations. The present result provides a new approach for constructing novel single-component NIR organic nanomedicines for multifunctional cancer therapy.

Exposure and risk assessment of volatile organic compounds and airborne phthalates in Singapore's Child Care Centers.

Infants and children under 6 years old spend most of daily time in Child Care Centers (CCCs), especially in the tropical regions like Singapore. Environmental exposure and associated risk during this early critical developmental stage is of great public concern. In this study, seven representative volatile organic compounds (VOCs) and five typical phthalates were analyzed in the indoor and outdoor air samples collected from 32 Singapore CCCs. The median of total VOC and phthalate concentration in indoor air was 19.03 and 5.41 µg m-3; respectively. For both indoors and outdoors environment, benzene, toluene and xylene were the dominant VOC contributors (more than 68%). For indoor air phthalates, di(2-ethylhexyl) phthalate and di-butyl phthalate (DBP) accounts for 60-76%. The level of both VOCs and phthalates in indoor environment was significantly higher than that in outdoor, with an average indoor/outdoor ratio of 1.24 and 1.45; respectively. A strong correlation (r > 0.50, p < 0.05) was observed between indoor and outdoor air compounds. VOC and phthalate levels have no significant difference between CCCs with split-unit and centrally ventilated air conditioners. Monte Carlo simulation was used to estimate exposure uncertainty and variability for the risk assessment. Overall, the concentrations of VOC were below the healthy reference values from either EPA Integrated Risk Information System (IRIS) or Singapore guideline. However, similar to other countries' report, benzene, DBP, ethylbenzene and naphthalene were at levels that could exceed the stringent standards such as Office of Environmental Health Hazard Assessment (OEHHA) cancer and reproductive health-based benchmarks.

[Identification of effective components from Naoxintong Capsules intestinal absorption liquid in inhibiting ADP-induced platelet aggregation].

Intestinal absorption liquid was prepared by using everted intestinal sac method; meanwhile, its recipes were decomposed or restructured. Platelet aggregation activity was examined by biochemical tests and a microplate reader. One or more kinds of Chinese medicines which displayed inhibiting activity in Naoxintong Capsules were screened through separation and combination of prescription. The results showed that Naoxintong Capsules could inhibit ADP-induced platelet aggregation. Recipe decomposition and restructuring results showed that Salviae Miltiorrhizae Radix et Rhizoma, Paeoniae Radix Rubra, Cinnamomi Ramulus and Hirudo were the main effective medicines in inhibiting platelet aggregation. Furthermore, Cinnamomi Ramulus played a vital role in inhibiting activity among those four kinds of Chinese medicines. Coumarin derived from intestinal absorption liquid of Cinnamomi Ramulus had inhibiting activity in the range of 50-200 µmol·L⁻¹, and other ingredients such as cinnamyl alcohol and cinnamaldehyde also had inhibiting activities. In conclusion, Salviae Miltiorrhizae Radix et Rhizoma, Paeoniae Radix Rubra, Cinnamomi Ramulus and Hirudo are the main components for inhibiting ADP-induced platelet aggregation, and Cinnamomi Ramulus has the most strongest inhibiting activity in Naoxintong Capsules.

Investigation of the use of serology and ultrasonography to detect hepatic cystic echinococcosis in Heilongjiang, China, using a Bayesian framework.

BACKGROUND: Cystic echinococcosis (CE) is a public health problem in China. However, the prevalence and incidence of CE in Heilongjiang province is still poorly understood. Because there is no perfect gold standard, evaluation of ultrasound (US) and serological methods have been limited. This study evaluated the use of these two diagnostic methods for the diagnosis of CE in suspected cases. METHODS: A total of 522 suspected hepatic CE patients, as well as their demographic and clinical features were collected and detected by immunoglobulin (IgG)-ELISA and US. The marginal posterior densities of sensitivity and specificity for both tests, and the prevalence of hepatic CE amongst participants, were estimated from the product of the likelihood function of observed and latent data by a Bayesian framework. RESULTS: Most of the patients were from rural areas. The most common symptom was upper abdominal pain. The antibody-positive proportion determined by IgG-ELISA was 24.33% (127/522), significantly higher than with US examination (17.24%, 90/522). Bayesian analysis indicated that the estimated prevalence of CE amongst suspected cases was 17.70% (95% credible interval: 14.23-21.54%). The sensitivity and specificity of the ELISA test were 92.63% and 90.37%, and that of US were 93.05% and 98.44%, respectively. Among US-confirmed hepatic CE cases, the male to female ratio was 0.46 and the peak age group was 40-49 years. CONCLUSIONS: The results of the current study demonstrate that CE is present in Heilongjiang province. They also suggest that, whilst ultrasonography appears to be the detection modality of choice, serology may have a use for detection of infection in individuals suspected to be infected. This may have applications for surveillance within the province.

Phthalocyanine-cRGD conjugate: synthesis, photophysical properties and in vitro biological activity for targeting photodynamic therapy.

An unsymmetrical phthalocyanine conjugated with an RGDyK moiety (6) was synthesized and characterized. Its photophysical properties, including electronic absorption, fluorescence emission (ΦF = 0.20), singlet oxygen quantum yield (ΦΔ = 0.63) and two-photon absorption cross section (TPACS) at different wavelengths were studied. The in vitro cell study data demonstrate that this Pc conjugate possesses significantly high cellular uptake toward the ανß3 positive DU145 prostate cancer cells along with an efficient photocytotoxicity (IC50 = 0.04 µM), showing this compound is one of the most promising photosensitizers for targeting photodynamic therapy (PDT) of cancer.

Chlorpromazine protects against apoptosis induced by exogenous stimuli in the developing rat brain.

BACKGROUND: Chlorpromazine (CPZ), a commonly used antipsychotic drug, was found to play a neuroprotective role in various models of toxicity. However, whether CPZ has the potential to affect brain apoptosis in vivo is still unknown. The purpose of this study was to investigate the potential effect of CPZ on the apoptosis induced by exogenous stimuli. METHODOLOGY: The ethanol treated infant rat was utilized as a valid apoptotic model, which is commonly used and could trigger robust apoptosis in brain tissue. Prior to the induction of apoptosis by subcutaneous injection of ethanol, 7-day-old rats were treated with CPZ at several doses (5 mg/kg, 10 mg/kg and 20 mg/kg) by intraperitoneal injection. Apoptotic cells in the brain were measured using TUNEL analysis, and the levels of cleaved caspase-3, cytochrome c, the pro-apoptotic factor Bax and the anti-apoptotic factor Bcl-2 were assessed by immunostaining or western blot. FINDINGS: Compared to the group injected with ethanol only, the brains of the CPZ-pretreated rats had fewer apoptotic cells, lower expression of cleaved caspase-3, cytochrome c and Bax, and higher expression of Bcl-2. These results demonstrate that CPZ could prevent apoptosis in the brain by regulating the mitochondrial pathway. CONCLUSIONS: CPZ exerts an inhibitory effect on apoptosis induced by ethanol in the rat brain, intimating that it may offer a means of protecting nerve cells from apoptosis induced by exogenous stimuli.