Type-I-interferon-responsive microglia shape cortical development and behavior.

Microglia are brain-resident macrophages that shape neural circuit development and are implicated in neurodevelopmental diseases. Multiple microglial transcriptional states have been defined, but their functional significance is unclear. Here, we identify a type I interferon (IFN-I)-responsive microglial state in the developing somatosensory cortex (postnatal day 5) that is actively engulfing whole neurons. This population expands during cortical remodeling induced by partial whisker deprivation. Global or microglial-specific loss of the IFN-I receptor resulted in microglia with phagolysosomal dysfunction and an accumulation of neurons with nuclear DNA damage. IFN-I gain of function increased neuronal engulfment by microglia in both mouse and zebrafish and restricted the accumulation of DNA-damaged neurons. Finally, IFN-I deficiency resulted in excess cortical excitatory neurons and tactile hypersensitivity. These data define a role for neuron-engulfing microglia during a critical window of brain development and reveal homeostatic functions of a canonical antiviral signaling pathway in the brain.

Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity.

Synapse remodeling is essential to encode experiences into neuronal circuits. Here, we define a molecular interaction between neurons and microglia that drives experience-dependent synapse remodeling in the hippocampus. We find that the cytokine interleukin-33 (IL-33) is expressed by adult hippocampal neurons in an experience-dependent manner and defines a neuronal subset primed for synaptic plasticity. Loss of neuronal IL-33 or the microglial IL-33 receptor leads to impaired spine plasticity, reduced newborn neuron integration, and diminished precision of remote fear memories. Memory precision and neuronal IL-33 are decreased in aged mice, and IL-33 gain of function mitigates age-related decreases in spine plasticity. We find that neuronal IL-33 instructs microglial engulfment of the extracellular matrix (ECM) and that its loss leads to impaired ECM engulfment and a concomitant accumulation of ECM proteins in contact with synapses. These data define a cellular mechanism through which microglia regulate experience-dependent synapse remodeling and promote memory consolidation.

Effectiveness of care bundles for prevention and treatment of postpartum hemorrhage: a systematic review.

OBJECTIVE: Care bundles are a promising approach to reducing postpartum hemorrhage-related morbidity and mortality. We assessed the effectiveness and safety of care bundles for postpartum hemorrhage prevention and/or treatment. DATA SOURCES: We searched MEDLINE, Embase, Cochrane CENTRAL, Maternity and Infant Care Database, and Global Index Medicus (inception to June 9, 2023) and ClinicalTrials.gov and the International Clinical Trials Registry Platform (last 5 years) using a phased search strategy, combining terms for postpartum hemorrhage and care bundles. STUDY ELIGIBILITY CRITERIA: Peer-reviewed studies evaluating postpartum hemorrhage-related care bundles were included. Care bundles were defined as interventions comprising ≥3 components implemented collectively, concurrently, or in rapid succession. Randomized and nonrandomized controlled trials, interrupted time series, and before-after studies (controlled or uncontrolled) were eligible. METHODS: Risk of bias was assessed using RoB 2 (randomized trials) and ROBINS-I (nonrandomized studies). For controlled studies, we reported risk ratios for dichotomous outcomes and mean differences for continuous outcomes, with certainty of evidence determined using GRADE. For uncontrolled studies, we used effect direction tables and summarized results narratively. RESULTS: Twenty-two studies were included for analysis. For prevention-only bundles (2 studies), low-certainty evidence suggests possible benefits in reducing blood loss, duration of hospitalization, and intensive care unit stay, and maternal well-being. For treatment-only bundles (9 studies), high-certainty evidence shows that the E-MOTIVE intervention reduced risks of composite severe morbidity (risk ratio, 0.40; 95% confidence interval, 0.32-0.50) and blood transfusion for bleeding, postpartum hemorrhage, severe postpartum hemorrhage, and mean blood loss. One nonrandomized trial and 7 uncontrolled studies suggest that other postpartum hemorrhage treatment bundles might reduce blood loss and severe postpartum hemorrhage, but this is uncertain. For combined prevention/treatment bundles (11 studies), low-certainty evidence shows that the California Maternal Quality Care Collaborative care bundle may reduce severe maternal morbidity (risk ratio, 0.64; 95% confidence interval, 0.57-0.72). Ten uncontrolled studies variably showed possible benefits, no effects, or harms for other bundle types. Nearly all uncontrolled studies did not use suitable statistical methods for single-group pretest-posttest comparisons and should thus be interpreted with caution. CONCLUSION: The E-MOTIVE intervention improves postpartum hemorrhage-related outcomes among women delivering vaginally, and the California Maternal Quality Care Collaborative bundle may reduce severe maternal morbidity. Other bundle designs warrant further effectiveness research before implementation is contemplated.

In Vitro and in Silico Study of New Biscoumarin Glycosides from Paramignya trimera against Angiotensin-Converting Enzyme 2 (ACE-2) for Preventing SARS-CoV-2 Infection.

In Vietnam, the stems and roots of the Rutaceous plant Paramignya trimera (Oliv.) Burkill (known locally as "Xáo tam phân") are widely used to treat liver diseases such as viral hepatitis and acute and chronic cirrhosis. In an effort to search for Vietnamese natural compounds capable of inhibiting coronavirus based on molecular docking screening, two new dimeric coumarin glycosides, namely cis-paratrimerin B (1) and cis-paratrimerin A (2), and two previously identified coumarins, the trans-isomers paratrimerin B (3) and paratrimerin A (4), were isolated from the roots of P. trimera and tested for their anti-angiotensin-converting enzyme 2 (ACE-2) inhibitory properties in vitro. It was discovered that ACE-2 enzyme was inhibited by cis-paratrimerin B (1), cis-paratrimerin A (2), and trans-paratrimerin B (3), with IC50 values of 28.9, 68, and 77 µM, respectively. Docking simulations revealed that four biscoumarin glycosides had good binding energies (∆G values ranging from -10.6 to -14.7 kcal/mol) and mostly bound to the S1' subsite of the ACE-2 protein. The key interactions of these natural ligands include metal chelation with zinc ions and multiple H-bonds with Ser128, Glu145, His345, Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots occur naturally in both cis- and trans-diastereomeric forms. The biscoumarin glycosides Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots hold potential for further studies as natural ACE-2 inhibitors for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Self-collection of samples for group B streptococcus testing during pregnancy: a systematic review and meta-analysis.

BACKGROUND: Sample self-collection for reproductive tract infection diagnosis has been found to offer greater convenience, privacy, autonomy, and expanded access to testing in non-pregnant adults. This review aimed to determine whether sample self-collection is as accurate as provider-collection for detection of group B streptococcus colonisation in pregnancy and whether a strategy of self-collection compared to provider-collection might improve maternal and neonatal health outcomes. METHODS: We searched CINAHL Plus, Medline, EMBASE, Maternity and Infant Care Database, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews in June 2022. Eligible studies compared self-collected and provider-collected samples taken from the same participants or participants randomised to either self-collection or provider-collection for reproductive tract infection testing using the same test and testing method in pregnant individuals. We included trials and observational studies. Reviewers assessed risk of bias using the QUADAS-2 checklist and independently extracted data. Sensitivity and specificity for group B streptococcus colonisation of self-collected compared to provider-collected samples were pooled using a bivariate, random-effects, meta-analytic model. This review was registered with PROSPERO (CRD42023396573). RESULTS: The search identified 5909 references, of which eleven diagnostic accuracy group B streptococcus studies were included (n = 3269 participants). No studies assessed the effects of self-collection in pregnancy on health outcomes. All studies had high or unclear risk of bias. Pooled sensitivities of self-collected samples for group B streptococcus detection were 82% (95% CI: 66-91%; I2 = 68.85%) in four trials (n = 1226) and 91% (95% CI: 83-96%; I2 = 37.38%) in seven non-randomised studies (n = 2043). Pooled specificities were 99% (95% CI: 98-99%; I2 = 12.08%) and 97% (95% CI: 94-99%; I2 = 72.50%), respectively. CONCLUSIONS: Self-collected samples for group B streptococcus detection in pregnancy had high specificity compared to provider-collection, but lower sensitivity, particularly for included trials. Studies investigating the effect of self-collection on health outcomes, and further higher quality trials comparing accuracy of self-collection to provider-collection, are required.

Component and Content of Lipid Classes and Phospholipid Molecular Species of Eggs and Body of the Vietnamese Sea Urchin Tripneustes gratilla.

Sea urchins (Tripneustes gratilla) are among the most highly prized seafood products in Vietnam because of their nutritional value and medicinal properties. In this research, lipid classes and the phospholipid (PL) molecular species compositions from the body and eggs of T. gratilla collected in Hon Tam, Nha Trang, Khanh Hoa, Vietnam, were investigated. Hydrocarbon and wax (HW), triacylglycerol (TG), mono- and diacylglycerol (MDAG), free fatty acid (FFA), sterol (ST), polar lipid (PoL), and monoalkyl-diacylglycerol are the major lipid classes. In PL, five main glycerophospholipid classes have been identified, in which 137 PL molecular species were detected in the body and eggs of T. gratilla, including 20 inositol glycerophospholipids (PI), 11 serine glycerophospholipids (PS), 22 ethanolamine glycerophospholipids (PE), 11 phosphatidic acids (PA), and 73 choline glycerophospholipids (PC). PI 18:0/20:4, PS 20:1/20:1, PE 18:1e/20:4, PA 20:1/20:1, and PC 18:0e/20:4 are the most abundant species with the highest content values of 38.65-48.19%, 42.48-44.41%, 41.21-40.03%, 52.42-52.60%, and 7.77-7.18% in each class of the body-eggs, respectively. Interestingly, PL molecules predominant in the body sample were also found in the egg sample. The molecular species with the highest content account for more than 40% of the total species in each molecular class. However, in the PC class containing 73 molecular species, the highest content species amounted to only 7.77%. For both the body and egg TL samples of the sea urchin T. gratilla, a substantial portion of C20:4n polyunsaturated fatty acid was found in PI, PE, and PC, but C16, C18, C20, and C22 saturated fatty acids were reported at low levels. The most dominant polyunsaturated fatty acid in PI, PE, and PC was tetracosapolyenoic C20, while unsaturated fatty acid C20:1 was the most dominant in PS and PA. To our knowledge, this is the first time that the chemical properties of TL and phospholipid molecular species of the PoL of Vietnamese sea urchin (T. gratilla) have been studied.

Boron Silicon B2Si3q and B3Si2p Clusters: The Smallest Aromatic Ribbons.

The small binary boron silicon clusters B2Si3q with q going from -2 to +2 and B3Si2p with p varying from -3 to +1 were reinvestigated using quantum chemical methods. The thermodynamic stability of these smallest ribbon structures is governed by both Hückel and ribbon models for aromaticity. The more negative the cluster charge, the more ribbon character is shown. In contrast, the more positive the charge state, the more pronounced the Hückel character becomes. The ribbon aromaticity character can also be classified into ribbon aromatic, semiaromatic, antiaromatic, and triplet aromatic when the electron configuration of a ribbon structure is described as [...π2(n+1)σ2n], [...π2n+1σ2n], [...π2nσ2n], and [...π2n+1σ2n-1], respectively. Geometry optimizations of the B2Si3 lowest-energy structure by some density functional theory (DFT) functionals result in a nonplanar shape because it possesses an antiaromatic ribbon character. However, its π aromaticity assigned by the Hückel rule is stronger in such a way that several other DFT and coupled-cluster theory CCSD(T) calculations show that B2Si3 is indeed stable in a planar form (Cs). A new global equilibrium structure for the anion B2Si32-, which is a ribbon semiaromatic species, was identified. Some benchmark tests were also carried out to evaluate the performance of popular methods for the treatment of binary B-Si clusters. At odds with some previous studies, we found that with reference to the high accuracy CCSD(T)/CBS method, the hybrid TPSSh functional is reliable for a structure search, whereas the hybrid B3LYP functional is more suitable for simulations of some experimental spectroscopic results.

Efficiency of a biodegradable gel containing hyaluronic acid and berberine hydrochloride in endoscopic sinus surgery (ESS): A prospective comparative study.

PURPOSE: To evaluate the efficiency of a biodegradable gel containing hyaluronic acid and berberine hydrochloride in endoscopic sinus surgery. METHODS: Sixty-six chronic rhinosinusitis patients with or without nasal polyps who underwent bilateral endoscopic sinus surgery (ESS) were randomly received a biodegradable gel containing hyaluronic acid and berberine hydrochloride or merocel in both middle meatal spacers at the end procedure of ESS. Lund-Kennedy endoscopic score (LKES) was used to examine status of nasal cavity on preoperative day and postoperative day 1 to 7. The LKES ratio was calculated as the LKES on postoperative day divided into the LKES on preoperative day. Visual analogue score (VAS) was used to assess patient's status from the first postoperative day to the hospital discharge day. The average VAS during hospital stays was calculated by the sum of VAS in each examination day divided into the number of examined day. The LKES ratio, the average of VAS during hospital stays and length of hospitalized day of the patients were used as clinical outcome indices in early stage after surgery. A general linear model adjusted for confounding factors was used for data analysis. RESULTS: Adjusted mean of LKES ratio were lower in group used biodegrable gel of hyaruloic acid and berberin hydrochlode (study group) than those in merocele group in the postoperative day 1 to day 7. However, significant difference was found in the adjusted mean of LKES ratio on the postoperative day 2 to 6. Similarly, the adjusted mean of VAS during hospital stays and length of hospitalized day after surgery in study group were significantly decreased as compared with those in merocele group. CONCLUSIONS: Biodegradable material containing hyaluronic acid and berberine hydrochloride was more effective than merocel in length of hospital stay, post-operative symptoms, and sinus cavity's status in early stage after ESS.

Essential Oils from the Leaves, Stem, and Roots of Blumea lanceolaria (Roxb.) Druce in Vietnam: Determination of Chemical Composition, and In Vitro, In Vivo, and In Silico Studies on Anti-Inflammatory Activity.

Blumea lanceolaria (Roxb.) Druce, a flowering plant, is used for treating cancer and inflammatory diseases. In this study, we determined the chemical composition of the EOs extracted from the leaves (LBEO), stem (SBEO), and roots (RBEO) of B. lanceolaria and analyzed their anti-inflammation potential. Overall, 30 compounds representing 99.12%, 98.44%, and 96.89% of total EO constituents of the leaves, stem, and roots, respectively, were identified using GC-MS. ELISA, Western blotting, and qRT-PCR studies showed that LBEO, SBEO, and RBEO inhibited multiple steps in the inflammatory responses in the RAW 264.7 cell model, including NO production; TNF-α, IL-6, iNOS, and COX-2 transcription and translation; and phosphorylation of IκBα and p65 of the NF-κB pathway. In the carrageenan-induced paw edema model, all three EOs inhibited paw edema at both early and delayed phases. Molecular docking studies indicated that the main components of B. lanceolaria EOs (BEOs) targeted and inhibited major components of inflammation-related pathways, including the arachidonic acid metabolic pathway, NF-κB pathway, and MAPK pathway. We present the first study to characterize the chemical composition of BEOs and confirm their potent anti-inflammatory effects in in vitro, in vivo, and in silico analysis. These results can facilitate the development of effective anti-inflammatory drugs with limited side effects in the future.

Reemergence of Human Monkeypox and Declining Population Immunity in the Context of Urbanization, Nigeria, 2017-2020.

A monkeypox outbreak in Nigeria during 2017-2020 provides an illustrative case study for emerging zoonoses. We built a statistical model to simulate declining immunity from monkeypox at 2 levels: At the individual level, we used a constant rate of decline in immunity of 1.29% per year as smallpox vaccination rates fell. At the population level, the cohort of vaccinated residents decreased over time because of deaths and births. By 2016, only 10.1% of the total population in Nigeria was vaccinated against smallpox; the serologic immunity level was 25.7% among vaccinated persons and 2.6% in the overall population. The substantial resurgence of monkeypox in Nigeria in 2017 appears to have been driven by a combination of population growth, accumulation of unvaccinated cohorts, and decline in smallpox vaccine immunity. The expanding unvaccinated population means that entire households, not just children, are now more susceptible to monkeypox, increasing risk of human-to-human transmission.

Cytotoxic components from the leaves of Erythrophleum fordii induce human acute leukemia cell apoptosis through caspase 3 activation and PARP cleavage.

Cassaine diterpenoids as erythrofordins A-C (1-3), pseudo-erythrosuamin (4), and erythrofordin U (5) isolated from the leaves of Vietnamese Erythrophleum fordii Oliver were tested cytotoxic activity against human leukemia cancer cells. The results showed that these metabolites exhibited dose-dependent cytotoxicity against human leukemia HL-60 and KG cells with IC50 values ranging from 15.2 ± 1.5 to 42.2 ± 3.6 µM. Treatment with erythrofordin B led to the apoptosis of HL-60 and KG cells due to the activation of caspase 3, caspase 9, and poly (ADP-ribose) polymerase (PARP). Erythrofordin B significantly increased Bak protein expression, but downregulated the anti-apoptotic protein Bcl-2, in HL-60 cells. In silico results demonstrated that erythrofordin B can bind to both the procaspase-3 allosteric site and the PARP-1 active site, with binding energies of -7.36 and -10.76 kcal/mol, respectively. These results indicated that the leaves of Vietnamese E. fordii, which contain cassaine diterpenoids, can induce the apoptosis of human leukemia cancer cells.

The binary boron lithium clusters B12Lin with n = 1-14: in search for hydrogen storage materials.

Molecular structures and properties of the binary clusters containing twelve boron atoms mixed with n lithium atoms, B12Lin with n = 1-14, were investigated using density functional theory with the TPSSh functional and the 6-311+G(d) basis set. Energetic parameters including relative energies, average binding energies and second-order energies of the entire series were predicted using the coupled-cluster theory (U)CCSD(T) in conjunction with the cc-pVTZ basis set. Several lowest-lying isomers were determined for each size B12Lin whose energies differ from each other by <3 kcal mol-1, except for n = 1, 2 and 4 (≤5 kcal mol-1), and particularly n = 8 (∼13 kcal mol-1). Electronic structure and chemical bonding in some specific sizes such as B12Li4, B12Li8 and B12Li14 were analyzed in detail. We established the electron shells of some magic clusters such as the B12Li4 cone for which we proposed a mixed cone-disk electron shell model. Thanks to both the phenomenological shell and Clemenger-Nilsson models, B12Li8 which contains a specific set of shells of 44 valence electrons is a high stability species. The arrangement of Li atoms around a fullerene B12 framework shows that the mixed B12Li8 emerges as the most suitable of this cluster series to adsorb molecular hydrogen. Up to 32 H2 molecules can strongly be attached to the B12Li8 cluster which is thus predicted to be a realistic candidate for hydrogen storage material with gravimetric density reaching up to a theoritical limit of 26 wt%. Attachment of the fifth H2 molecule to each Li atom of B12Li8 results in weaker average bonds but can give rise to a total of 40 H2 molecules, corresponding to 30 wt% of hydrogen.

An On-Demand Charging for Connected Target Coverage in WRSNs Using Fuzzy Logic and Q-Learning.

In wireless rechargeable sensor networks (WRSNs), a mobile charger (MC) moves around to compensate for sensor nodes' energy via a wireless medium. In such a context, designing a charging strategy that optimally prolongs the network lifetime is challenging. This work aims to solve the challenges by introducing a novel, on-demand charging algorithm for MC that attempts to maximize the network lifetime, where the term "network lifetime" is defined by the interval from when the network starts till the first target is not monitored by any sensor. The algorithm, named Fuzzy Q-charging, optimizes both the time and location in which the MC performs its charging tasks. Fuzzy Q-charging uses Fuzzy logic to determine the optimal charging-energy amounts for sensors. From that, we propose a method to find the optimal charging time at each charging location. Fuzzy Q-charging leverages Q-learning to determine the next charging location for maximizing the network lifetime. To this end, Q-charging prioritizes the sensor nodes following their roles and selects a suitable charging location where MC provides sufficient power for the prioritized sensors. We have extensively evaluated the effectiveness of Fuzzy Q-charging in comparison to the related works. The evaluation results show that Fuzzy Q-charging outperforms the others. First, Fuzzy Q-charging can guarantee an infinite lifetime in the WSRNs, which have a sufficient large sensor number or a commensurate target number. Second, in other cases, Fuzzy Q-charging can extend the time until the first target is not monitored by 6.8 times on average and 33.9 times in the best case, compared to existing algorithms.

Anti-inflammatory xanthone derivatives from Garcinia delpyana.

Two new xanthones delpyxanthone A (1) and delpyxanthone B (3), together with four known ones, gerontoxanthone I (2), α-mangostin (4), cowanin (5) and cowanol (6) were isolated from the stem bark of Garcinia delpyana. The chemical structures of 1-6 were established mainly using nuclear magnetic resonance (NMR) and mass spectrometry (MS). The anti-inflammatory activity of the isolated compounds was evaluated against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells in vitro. Compounds 1-4 showed significant inhibitory activity against the LPS-induced NO production in RAW264.7 cells with IC50 values ranging from 14.5 to 28.2 µM, but the others were inactive. The results suggested that G. delpyana and its constituents might be potential anti-inflammatory agents on RAW 264.7 cells.[Formula: see text].

On the Inhibitability of Natural Products Isolated from Tetradium ruticarpum towards Tyrosine Phosphatase 1B (PTP1B) and α-Glucosidase (3W37): An In Vitro and In Silico Study.

Folk experiences suggest natural products in Tetradium ruticarpum can be effective inhibitors towards diabetes-related enzymes. The compounds were experimentally isolated, structurally elucidated, and tested in vitro for their inhibition effects on tyrosine phosphatase 1B (PTP1B) and α-glucosidase (3W37). Density functional theory and molecular docking techniques were utilized as computational methods to predict the stability of the ligands and simulate interaction between the studied inhibitory agents and the targeted proteins. Structural elucidation identifies two natural products: 2-heptyl-1-methylquinolin-4-one (1) and 3-[4-(4-methylhydroxy-2-butenyloxy)-phenyl]-2-propenol (2). In vitro study shows that the compounds (1 and 2) possess high potentiality for the inhibition of PTP1B (IC50 values of 24.3 ± 0.8, and 47.7 ± 1.1 µM) and α-glucosidase (IC50 values of 92.1 ± 0.8, and 167.4 ± 0.4 µM). DS values and the number of interactions obtained from docking simulation highly correlate with the experimental results yielded. Furthermore, in-depth analyses of the structure-activity relationship suggest significant contributions of amino acids Arg254 and Arg676 to the conformational distortion of PTP1B and 3W37 structures overall, thus leading to the deterioration of their enzymatic activity observed in assay-based experiments. This study encourages further investigations either to develop appropriate alternatives for diabetes treatment or to verify the role of amino acids Arg254 and Arg676.

A Path-Length Efficient, Low-Overhead, Load-Balanced Routing Protocol for Maximum Network Lifetime in Wireless Sensor Networks with Holes.

In wireless sensor networks (WSNs) with holes, designing efficient routing protocols, which prolong the network lifetime, is one of the most critical issues. To this end, this paper proposes a new geographic routing protocol for WSNs named the load Balanced and constant Stretch protocol for bypassing Multiple Holes (i.e., BSMH). In contrast to the existing works in the literature, the design of BSMH simultaneously takes into account the three factors that impacted the network lifetime, including routing path length, control packet overhead, and load balance among the nodes. Moreover, BSMH aims at minimizing the routing path length and the control overhead, while maximizing the load balance. We theoretically prove the efficiency of BSMH and extensively evaluate BSMH against the state-of-the-art protocols. The evaluation results show that the proposed protocol outperforms the others in various investigated metrics, not only network lifetime, but also routing path stretch, load balance, and control overhead. Specifically, BSMH prolongs the network lifetime by 30 % compared to the existing protocols while guaranteeing that the routing path stretch is under 1 . 3 .

Antioxidant and Cell Proliferation Properties of the Vietnamese Traditional Medicinal Plant Peltophorum pterocarpum.

Peltophorum pterocarpum is regarded as one of the most important medicinal plants in the traditional medicine system of Vietnam. However, scientific evidence for the antioxidant effects against lipid peroxidation and the potential effects in cancer of this plant are lacking. In our experiments, 70% ethanolic extracts of P. pterocarpum leaves (LPP) and stem bark (SPP) were evaluated for their low-density lipoprotein (LDL) oxidation and cytotoxic activity against cancer cell lines. Both LPP and SPP inhibited Cu2+-mediated LDL by increasing the lag time of conjugated diene formation and inhibiting the generation of thiobarbituric acid reactive substances (TBARS) in a dose-dependent manner. In cancer cells, LPP and SPP triggered the most potent cytotoxic effects against human leukemia cells, CRF-SBA and HL-60, with half-maximal inhibitory concentration (IC50) values ranging from 118.5 to 157.2 µg/mL. SPP exhibited significant cytotoxicity against MIA PACA2, A549, and KG cell lines with IC50 values of 167.5, 244.1 and 255.0 µg/mL, respectively. Meanwhile, LPP showed cytotoxic activity against KG with an IC50 value of 228.1 µg/mL. SPP mediated cytotoxicity in HL-60 and CCRF-SBA cells through the activation of the apoptosis pathway, including the activation of caspases 3, and 9 and poly (ADP-ribose) polymerase (PARP). These results suggested that SPP may prevent the development and progression of atherosclerosis and leukemia in humans.

Cassaine Diterpenoid Amide from Stem Bark of Erythrophleum fordii Suppresses Cytotoxic and Induces Apoptosis of Human Leukemia Cells.

Cassaine diterpenoids amides from the stem bark of Vietnamese Erythrophleum fordii Oliver were screened for their cytotoxic activity against human cancer cells. The cell proliferation assay results showed that, among the active compounds, 3ß-acetyl-nor-erythrophlamide (3AEP) exhibited the most potential cytotoxicity against human leukemia HL-60 and KG cells with IC50 values of 12.0 ± 1.2 and 18.1 ± 2.7 µM, respectively. Treatment of 3AEP resulted in the apoptosis of HL-60 cells via the activation of caspase 3, and poly (ADP-ribose) polymerase (PARP). Molecular docking in silico results showed that the 3AEP can bind to both the procaspase-3 allosteric site and the PARP-1 active site, with binding energies of -7.51 and -9.63 kcal/mol respectively. These results indicated that the stem bark of Vietnamese E. fordii and its cassaine diterpenoid amides may be useful in the apoptosis induction of human leukemia cancer cells.

Phosphoproteomic profiling of mouse primary HSPCs reveals new regulators of HSPC mobilization.

Protein phosphorylation is a central mechanism of signal transduction that both positively and negatively regulates protein function. Large-scale studies of the dynamic phosphorylation states of cell signaling systems have been applied extensively in cell lines and whole tissues to reveal critical regulatory networks, and candidate-based evaluations of phosphorylation in rare cell populations have also been informative. However, application of comprehensive profiling technologies to adult stem cell and progenitor populations has been challenging, due in large part to the scarcity of such cells in adult tissues. Here, we combine multicolor flow cytometry with highly efficient 3-dimensional high performance liquid chromatography/mass spectrometry to enable quantitative phosphoproteomic analysis from 200 000 highly purified primary mouse hematopoietic stem and progenitor cells (HSPCs). Using this platform, we identify ARHGAP25 as a novel regulator of HSPC mobilization and demonstrate that ARHGAP25 phosphorylation at serine 363 is an important modulator of its function. Our approach provides a robust platform for large-scale phosphoproteomic analyses performed with limited numbers of rare progenitor cells. Data from our study comprises a new resource for understanding the molecular signaling networks that underlie hematopoietic stem cell mobilization.

Isolation of Campylobacter Species from Stool Samples by Use of a Filtration Method: Assessment from a United States-Based Population.

Fecal samples submitted to our clinical microbiology laboratory from patients in the Philadelphia region were prospectively analyzed for Campylobacter species other than C. jejuni and C. coli using a filtration method and microaerobic conditions with increased H2 concentrations. Of 225 samples tested, 13 (5.8%) yielded Campylobacter species, with frequent isolation of C. concisus The majority of Campylobacter species were not clinically significant. Additional studies in U.S. populations are warranted.