Gelsemine is an important toxic substance extracted from Gelsemium elegans, which has a lot of biological functions in cells and organisms, but its toxicity has been rarely reported in Tetrahymena thermophila. In this study, we used the protozoan T. thermophila as an experimental model to investigate the potential toxicity-induced mechanism of gelsemine in the unicellular eukaryote. Our results clearly showed gelsemine inhibited T. thermophila growth in a dose-dependent manner. This exposure also resulted in oxidative stress on T. thermophila cells and antioxidant enzyme levels were significantly altered at high gelsemine levels (p < 0.05). Gelsemine produced a slight apoptotic effect at the highest (0.8 mg/mL) gelsemine level used here (p < 0.05). Furthermore, the toxin-induced DNA damage in a dose-dependent manner. The ultrastructural analysis also revealed mitophagic vacuoles at 0.4 and 0.8 mg/mL levels of gelsemine exposure. Moreover, expressions of oxidative stress-related and MAP kinase genes were significantly changed after exposure to 0.8 mg/mL level of gelsemine (p < 0.05). Altogether, our results clearly show that gelsemine from G. elegans can inhibit the growth via inducing oxidative stress and DNA damage in T. thermophila cells.

Mitochondrial genomes (mitogenomes) of five Cyrtodactylus were determined. Their compositions and structures were similar to most of the available gecko lizard mitogenomes as 13 protein-coding, two rRNA and 22 tRNA genes. The non-coding control region (CR) of almost all Cyrtodactylus mitogenome structures contained a repeated sequence named the 75-bp box family, except for C. auribalteatus which contained the 225-bp box. Sequence similarities indicated that the 225-bp box resulted from the duplication event of 75-bp boxes, followed by homogenization and fixation in C. auribalteatus. The 75-bp box family was found in most gecko lizards with high conservation (55-75% similarities) and could form secondary structures, suggesting that this repeated sequence family played an important role under selective pressure and might involve mitogenome replication and the likelihood of rearrangements in CR. The 75-bp box family was acquired in the common ancestral genome of the gecko lizard, evolving gradually through each lineage by independent nucleotide mutation. Comparison of gecko lizard mitogenomes revealed low structural diversity with at least six types of mitochondrial gene rearrangements. Cyrtodactylus mitogenome structure showed the same gene rearrangement as found in most gecko lizards. Advanced mitogenome information will enable a better understanding of structure evolution mechanisms.

Cancer stem cells (CSCs) are proposed to account for the initiation of cancer metastasis, but their accessibility remains a great challenge. This study reports deep tumor-penetrated biomimetic nanocages to augment the accessibility to CSCs fractions in tumor for anti-metastasis therapy. The nanocages can load photothermal agent of 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DBN) and chemotherapeutic epirubicin (EBN) to eradicate CSCs for photothermal-chemotherapy of breast cancer metastasis. In metastatic 4T1-indcued tumor model, both DBN and EBN can efficiently accumulate in tumor sites and feasibly permeate throughout the tumor mass. These biomimetic nanosystems can be preferentially internalized by cancer cells and effectively accessed to CSCs fractions in tumor. The DBN+laser/EBN treatment produces considerable depression of primary tumor growth, drastically eradicates around 80% of CSCs fractions in primary tumor, and results in 95.2% inhibition of lung metastasis. Thus, the biomimetic nanocages can be a promising delivery nanovehicle with preferential CSCs-accessibility for effective anti-metastasis therapy.

Several studies have investigated the prevalence of Alzheimer's disease (AD) among the general population in several parts of China. However, the results have been inconsistent. This meta-analysis was conducted to estimate the overall prevalence of AD between 2007 and 2017 in China.

Evidence of increased type 2 diabetes (T2D) risk associated with potatoes consumption is equivocal. We aimed to perform a meta-analyses on the association between potatoes consumption and T2D risk in prospective cohort studies.

Background: Long-term sickness absence is a growing concern in Belgium and other European countries. Since 2017, Belgian physicians of the sickness funding organisations are required to assess the re-integration possibilities within the first two months of sickness absence. Given the shortage of physicians in the assessment of work disability and the growing number of people in sickness absence, there is a need for a triage tool, allowing to assign return-to work support to patients having a high-risk profile not to resume work. Methods/design: The current study comprises a comprehensive validation process of a screening tool that supports Belgian physicians in guiding people back to work. The study consists of a theoretical construct validation (face validity and content validity), and an empirical construct validation (concurrence validity, factorial validity, predictive validity, hypothesis testing validity and known- group validity). Expected impact of the study for Public Health: The screening instrument assessing the risk for long-term sickness absence is a tool developed to support physicians who work for sickness funds and for occupational health and safety organisations. Both professionals play an important role in the return to work process and the prevention of long-term sickness absence. The screening tool aims at making a distinction between people who will resume their work independently and people who will need support to do so. Generation of this prediction model will help physicians to focus effort and resources in the high-risk group. Results may also help understand the relationship between the biopsychosocial model and long-term sick-leave.

(±)-Peniorthoesters A and B (±1 and ±2), two pairs of unprecedented spiro-orthoester enantiomers with a 1,4,6-trioxaspiro[4. 5]decane-7-one unit, were obtained from Penicillium minioluteum. Their structures were determined by spectroscopic methods, X-ray diffraction analyses, and ECD calculations. (±)-Peniorthoesters A and B are the first examples of spiro-orthoester enantiomers, and they represent the first spiro-orthoesters originating from fungi. All compounds showed potential inhibitory activities comparable to dexamethasone against NO production with IC50 values ranging from 14.2 to 34.5 μM.

Excess body weight has been causally linked to an increased risk of different cancer types, including colorectal cancer (CRC) but the mechanisms underlying this association are practically unknown. We investigate redox state-superoxide (SO) generation rate, activity of complex I in electron transport chain (ETC) of mitochondria and of dinitrosyl iron complexes by electron paramagnetic resonance; activity of matrix metalloproteinase (gelatinase) MMP-2 and MMP-9 by gel zymography of adipose tissues (AT) from 46 patients (64.0 ± 1.6 y.o.) with CRC (II-III stages, pT2-3N0-2M0) in the AT adjacent to tumor (ATAT) and at a distance of 3 cm from the tumor (ATD) to follow the connection of the AT redox state with some of the tumor microenvironment indicators. We have incubated the AT species with the tumor necrosis factor α (TNF-α) to follow its influence on the measured values. As a control, normal AT (NAT) obtained during the liposuction is used. Tumor-induced changes in mitochondrial ETC of ATAT, particularly for Complex I, lead to the enhanced SO generation and consequent oxidative modifications of DNA in ATAT (up to 6.1 times higher than that in NAT and 3.7 times higher than that in ATD, p < 0.05). Gelatinase activity in ATAT is significantly higher than in ATD. A considerable effect of TNF-α on ATAT and ATD (but not on NAT, i.e., only on the tissues where the reprogramming of metabolism has already occurred under the influence of tumor) manifested in increase of cellular hypoxia, gelatinase activity, and SO generation rate is observed. The results can be used for better understanding the mechanism(s) of metabolic symbiosis of tumor and AT as well as serving as a basis for new therapeutic approaches.

IFN-γ and IL-22 are deeply involved in the pathogenesis of psoriasis, as they boost the expression of inflammatory genes and alter proliferative and differentiative programs in keratinocytes. The JAK1/JAK2/STAT1 and JAK1/TYK2/STAT3 pathways triggered by IFN-γ and IL-22, respectively, are aberrantly activated in psoriasis, as highlighted by the peculiar STAT1 and STAT3 signatures in psoriatic skin lesions. To limit the detrimental consequences of IFN-γ and IL-22 excessive stimulation, psoriatic keratinocytes activate suppressor of cytokine signaling (SOCS)1 and SOCS3, which in turn dampen molecular signaling by inhibiting JAK1 and JAK2. Thus, JAK targeting appears to be a reasonable strategy to treat psoriasis. Tofacitinib is an inhibitor of JAK proteins, which, similarly to SOCS, impedes JAK phosphorylation. In this study, we evaluated the immunomodulatory effects of tofacitinib on epidermal keratinocytes in in vitro and in vivo models of psoriasis. We demonstrated the selectivity of tofacitinib inhibitory action on IFN-γ and IL-22, but not on TNF-γ or IL-17 proinflammatory signaling, with suppressed expression of IFN-γ-dependent inflammatory genes, and restoration of normal proliferative and differentiative programs altered by IL-22 in psoriatic keratinocyte cultures. Tofacitinib also potently reduced the psoriasiform phenotype in the imiquimod-induced murine model of psoriasis. Finally, we found that tofacitinib mimics SOCS1 or SOCS3 activities, as it impaired the same molecular pathways in IFN-γ or IL-22-activated keratinocytes.

We discuss 3 patients presenting with pneumonia associated with nonencapsulated Streptococcus pneumoniae (NESp), an emerging pathogen commonly causing upper respiratory infections. Clinical isolates obtained from these patients were characterized to evaluate their respective antibiotic resistance and virulence mechanisms. We demonstrate that NESp resistant to classical drug treatments are isolated during pneumonia.

The sympathetic nervous system is a major efferent pathway through which the central nervous system controls the function of peripheral organs. Genetic and pharmacologic evidence in mice indicated that stimulation of the β2 adrenergic receptor (β2AR) in osteoblasts promotes bone loss, leading to the paradigm that high sympathetic nervous activity is deleterious to bone mass. However, considerably less data exist to understand the putative impact of endogenous norepinephrine (NE), released by sympathetic nerves, on bone homeostasis. In this study, we investigated the in vivo expression and activity of the norepinephrine transporter (NET), a membrane pump known to actively uptake NE from the extracellular space in presynaptic neurons. Consistent with previously published in vitro data showing NET uptake activity in differentiated osteoblasts, we were able to detect active NET-specific NE uptake in the mouse cortical bone compartment in vivo. This uptake was the highest in young mice and accordingly with an age-related reduction in NET uptake, NE bone content increased whereas Net RNA and protein expression decreased with age. Histologically, NET expression in adult mouse bones was detected in osteocytes via immunofluorescence. Lastly, taking advantage of tissue-specific fluorescent reporter mice, we used CLARITY imaging and light sheet microscopy to visualize the 3D distribution of sympathetic fibers in whole mount preparations of bone tissues. These analyses allowed us to detect tyrosine hydroxylase (TH)-positive sympathetic nerve fibers penetrating the cortical bone, where NET+ osteocytes reside. Together, these in vitro results support the existence of an age-dependent extraneuronal and osteocytic function of NET with potential to buffer the bone catabolic action of endogenous NE released by sympathetic nerves in vivo.

Transurethral resection of a bladder tumor (TURBT) using a resectoscope has been standard treatment for bladder cancer. However, no treatment method promotes the repair of resected bladder tissue. The aim of this study was to examine the healing process of damaged bladder tissue after a transurethral injection of bone marrow mesenchymal stem cells (MSCs) into the bladder. An injection of magnetic MSCs meant that they accumulated in the damaged area of the bladder. Another aim of this study was to compare the acceleration effect of MSC magnetic delivery on the repair of bladder tissue with that of non-magnetic MSC injection.

In this article, using human pancreatic cancer cell lines and tumor specimens, we analyze the expression and localization of the invadopodia-related proteins TKS5 and Cortactin. Specifically, we present data on: a) TKS5 expression and localization by immunofluorescence in human pancreatic tumors, b) Cortactin expression by western blotting in various human pancreatic adenocarcinoma cell lines, c) TKS5 and Cortactin localization at invadopodia in BxPC-3 pancreatic adenocarcinoma cells, and d) TKS5 and Cortactin localization by co-immunofluorescence in human pancreatic cancer specimens. Data presented here is related to and supportive of the research article by Chen et al., "TKS5-positive invadopodia-like structures in human tumor surgical specimens" (Chen et al., 2019), where interpretation of the research data presented here is available.

This study aimed to examine the validity and internal consistency of Arabic version of the Cornell Scale for Depression in Dementia (A-CSDD) and compare it to the Geriatric Depression and Hospital Anxiety and Depression Scales.

Apolipoprotein E4 (apoE4) is the predominant risk factor for late-onset Alzheimer's disease (AD), but the question of which structural differences might explain its effect remains unclear.

The degeneration of memory-focused synapses play important roles in Alzheimer's disease (AD) pathogenesis, while it is not well known how β amyloid interferes neuron apoptosis and how a herbal combination GAPT influence synapse loss and neuronal apoptosis pathways of APP/PS1 transgenic mice.

Purpose: Transgender (trans) and nonbinary (NB) individuals experience a number of health and health care disparities when compared with cisgender individuals. While this has been reflected in nationwide surveys of trans/NB people in the United States, few studies capture the unique experiences of trans people living in the South, and fewer studies have collected qualitative data directly from trans/NB people. The purpose of this trans/NB-led initiative was to engage the trans/NB community in a southern state in defining their most pressing health and health care concerns and comparing those results with those reported by their cisgender allies, as well as national samples of trans individuals. Methods: Participants (n=125), who were trans/NB individuals (77%) and their cisgender allies (23%) living in a southern state, completed a survey with open-ended response options and/or participated in trans-led summits. Results: The top three health and health care concerns identified by participants, both trans/NB and cisgender allies, were insurance coverage for transition-related care, access to and availability of transition-related care, and education of health care providers about trans patients and issues. Conclusions: The top concerns from trans/NB participants and cisgender allies reflect health and health care issues frequently reported by the trans/NB community nationwide. Having qualitative data from trans/NB individuals and their allies living in the South enhances our understanding of these commonly reported concerns. Future research, education, and health care practice initiatives should focus on the concerns identified by the trans/NB community.

Alcohol consumption is considered to be a major health problem among people living with HIV/AIDS. Our previous reports have shown that ethanol reduced intracellular concentrations of antiretroviral drugs elvitegravir and darunavir in the HIV-1-infected U1 cell line. Ethanol also increased HIV-1 replication despite the presence of elvitegravir. Our previous finding has also shown that the levels of cytochrome P450 enzyme 2E1 (CYP2E1) and oxidative stress in blood monocytes were induced, while the concentration of alcohol in the plasma was reduced in HIV-1-infected alcohol users compared to uninfected alcohol users. However, the role of CYP2E1 in ethanol-enhanced oxidative stress and HIV-1 replication is still unclear.

Although rare, cutaneous lymphomas represent a separate entity in hematologic oncology. T cell origin lymphomas are most common, with Mycosis Fungoides (MF) accounting for about 50-70% of cases. Sezary Syndrome (SS), which represents the leukemic varian of MF, accounts for 3% of Cutaneous T Cell Lymphomas (CTCL). Total Skin Electron Beam Therapy (TSEB) is included at the mainstream of treatment choices for CTCL. The scope of this study is to evaluate the effectiveness and toxicity of two treatment schedules of TSEB.

Spastic paraplegia 30 is a recently established autosomal recessive disease characterized by a complex form of spastic paraplegia associated with neuropathy. Homozygous mutations of KIF1A reportedly lead to hereditary spastic paraplegia or hereditary sensory and autonomic neuropathy type 2 (HSAN2), whereas heterozygous mutations can cause nonsyndromic and syndromic intellectual disability (MRD9). Here we report the case of a 37-year-old female who presented with gait disturbance complicated with moyamoya disease.