Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer’s disease

Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer’s disease.Citri Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases,including Parkinson’s and Huntington’s diseases,however,the effect of Citri Reticulatae Semen on Alzheimer’s disease remains unelucidated.In the current study,the anti-apoptotic and autophagic roles of Citri Reticulatae Semen extract on amyloid-beta-induced apoptosis in PC12 cells were first investigated.Citri Reticulatae Semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of autophagy.In addition,Citri Reticulatae Semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro,and suppress amyloid-beta-induced pathology such as paralysis,in a transgenic Caenorhabditis elegans in vivo model.Moreover,genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae Semen extract was autophagy-dependent.Most importantly,Citri Reticulatae Semen extract was confirmed to improve cognitive impairment,neuronal injury and amyloid-beta burden in 3×Tg Alzheimer’s disease mice.As revealed by both in vitro and in vivo models,these results suggest that Citri Reticulatae Semen extract is a potential natural therapeutic agent for Alzheimer’s disease via its neuroprotective autophagic effects.

Targeting calcium signaling in Alzheimer’s disease: challenges and promising therapeutic avenues

The critical role of calcium dyshomeostasis in the pathogenesis of Alzheimer’s disease(AD):AD is a progressive neurodegenerative disease characterized by cognitive decline,memory impairment,and behavioral changes.With an estimated 50 million people being affected worldwide,the incidence of AD is constantly increasing globally.The hallmark of AD is the accumulation of amyloid-beta protein(Aβ)in the form of amyloid plaques and hyperphosphorylated tau protein in the form of neurofibrillary tangles.However,increasing evidence suggests that calcium ion(Ca2+)dysregulation also plays a crucial role in the pathogenesis of AD(Calvo-Rodriguez and Bacskai,2021).As a key second messenger,Ca2+regulates a wide range of cellular processes,including the release of neurotransmitters,gene expression,and cell death.Ca^(2+)also regulates the activity of Calcium/calmodulin-dependent protein kinase II,which is critical for synaptic plasticity,learning,and memory(Kaushik et al.,2022).Alternation in the Ca^(2+)signal is an early event in the pathogenesis of AD,which can lead to synaptic dysfunction,neuronal loss,and cognitive impairment.

Iodine 131 Treatment in Graves’ Disease in a West African Country: Preliminary Study about 25 Cases in Senegal

Introduction: Graves’ disease is the most common cause of hyperthyroidism. Its treatment uses synthetic antithyroid drugs but the use of aggressive radical therapy such as surgery or non-aggressive therapy such as iodine-131 is not uncommon. Treatment of Graves’ disease with radioactive iodine or iratherapy is a simple, inexpensive, well-tolerated treatment. It was introduced in Senegal in 2016. We report through this work the preliminary assessment of the only nuclear medicine service in Senegal in the management of Graves’ disease by iodine-131. Patients and Methods: Retrospective study of the first cases of Graves’ disease treated with iratherapy in Senegal. Socio-demographic, clinical, paraclinical, therapeutic and evolutionary aspects were studied. Radiation protection rules have been implemented and contraception has been effective for six months in women of childbearing age. Results: 25 patients were collected with a mean age of 45 years, twenty women (80%), a family goiter in 24% and a psycho-affective context in 64% of cases. Thyrotoxicosis syndrome was associated with goiter in 68% of patients and exophthalmos in 64%. Thyroid ultrasound performed in 20 patients showed vascular goiter in 80% and thyroid scintigraphy in 3 patients, homogeneous and diffuse hyperfixation. TRAK dosed in 8 patients was still positive. All patients had received first-line medical treatment. The average duration of this treatment was more than 18 months in 92%. The empirically used iodine-131 activity averaged 15.35 mCi. Oral corticosteroid therapy was prescribed in 7 patients for the prevention of malignant orbitopathy. No early side effects were noted. The remission rate at 3 months was 52% and at 6 months was 88% to 92%. Conclusion: The effectiveness of radioactive iodine, in particular ablative doses in the treatment of hyperthyroidism, is no longer to be demonstrated. Taking into account our socioeconomic context, iratherapy should be a treatment of choice for hyperthyroidism with a good quality/price ratio and excellent tolerance.

Cold and Fertile: Cryopreservation as an Innovative Tool in Addressing Challenges in Teratozoospermia

Teratozoospermia is an infertility issue that affects a significant number of couples of reproductive age. One of the potential causes contributing to the global decline in seminal quality includes factors such as diet, alcohol and tobacco consumption, high levels of stress, and environmental influences. This underscores the need to preserve the fertility of these patients through cryopreservation techniques. In this review, we explore the latest methods for freezing seminal samples, highlighting their advancements and advantages in addressing the challenge of perpetuating animal species, particularly in the context of human infertility.

Contribution of Bone Scintigraphy in the Metastatic Extension Assessment of Prostate Cancer: A Study of 288 Cases in the Nuclear Medicine Department of Idrissa Pouye General Hospital, Dakar

Introduction: Prostate cancer is the most frequently diagnosed male malignancy and the fifth leading cause of cancer death in men worldwide. Since the advent of screening methods such as Prostate Specific Antigen (PSA) assay, digital rectal examination (DRE) and prostate biopsy, its incidence has increased significantly. The aim of our study was to analyse aspects of bone scintigraphy (BS) as part of the metastatic extension assessment of prostate cancer in Senegal. Patients and Methods: This was a retrospective descriptive and analytical study, running from January 1er 2022 to August 31 2023. Patients with histologically confirmed prostate cancer were included. Whole-body scans (WBS) were performed using a dual-head SPECT gamma camera (Mediso Nucline TM Spirit DH-V type), 3 hours after intravenous injection of 8 MBq/kg (555 to 740 MBq) of 99mTc-HMDP. Results: A total of 288 patients with a mean age of 68.37 ± 7.79 years were included. The median total PSA level was 97.6 ng/ml, with 144 patients having a level greater than or equal to 20 ng/ml. All patients had adenocarcinoma, and the Gleason score was available in 202 (70.13%) patients, 75.75% of whom had a score greater than or equal to 7. BS was contributory in 70.48% of cases, with 30.90% positive and 39.58% negative. The result was inconclusive in 85 patients (29.51%). The mean PSA for patients with a positive scan was 190.2 ng/ml and 40.6 ng/ml for those with a negative scan. Multiple metastatic lesions predominated (87.35% of cases). Metastatic lesions occurred preferentially in the axial skeleton, with a proportion of 68% versus 32% in the appendicular skeleton. Classification of bone metastases according to the SOLOWAY score revealed grade I (62.07%), grade II (35.63%) and grade IV (2.30%). Conclusion: In Senegal, prostate cancer is generally diagnosed in men of advanced age. The presence of bone metastases is frequent in its evolution, transforming a curable localized disease into a generalized disease with a compromised prognosis. Bone scintigraphy remains an essential part of the initial work-up and evaluation of response to treatment.

Contribution of Bone Scintigraphy in the Diagnosis of a Case of SAPHO in the Nuclear Medicine Department of Idrissa Pouye General Hospital (Dakar, Senegal)

Introduction: The acronym SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis) is a syndrome combining osteoarticular and cutaneous manifestations. It occurs mainly between the ages of 30 and 50. Sternocostoclavicular hyperostosis is one of the main distinguishing features. We report a case of SAPHO in Dakar diagnosed by bone scintigraphy. Observation: 28-year-old Senegalese women presented with left shoulder pain and relative functional impotence for over 2 years. Examination revealed right sternoclavicular hyperostosis and left shoulder pain on palpation. Questioning revealed a history of acne and hyperostosis of the right first toe. Bone scintigraphy, performed after injection of 630 MBq of 99mTc-HMDP, revealed: hyperfixation of the bilateral (right++) manubrio-sternal and sternoclavicular junction, producing the classic bull’s horn image;hyperfixation of the left shoulder with an inflammatory appearance;hyperfixation of the sacroiliac joints suggestive of bilateral sacroiliitis;hyperfixation of the right first toe;two mandibular hyper fixations probably related to dental damage. This scintigraphic appearance in one was strongly suggestive of SAPHO syndrome. Conclusion: SAPHO syndrome, related to spondyloarthropathy, associates cutaneous and osteoarticular signs. It is characterized by frequent delays in diagnosis due to poor recognition. Soy is an invaluable diagnostic tool, enabling us to assess the extent of the disease and its evolution.

Application of a Pulsed Electric Field to Modify the Free Energy of the Active Site of an Azoreductase

The Gibbs free energy is strongly related to the stability and catalytic function of an enzyme through the energetic changes that occur in the chemical reactions the enzyme catalyzes. In this in silico study, a pulsed electric field was applied to an azoreductase, and its effect on the Gibbs free energy of molecular docking with two dyes was measured. We propose that certain stimuli from a pulsed electric field favor the structural stability of the enzyme by promoting an arrangement in the active site, potentially leading to an enhancement of enzymatic activity overall.

Place of Bone Scintigraphy in the Assessment of Extension and Follow-Up of Breast Cancer in Senegal: Study of 165 Cases in the Nuclear Medicine Department of Idrissa Pouye General Hospital (Dakar)

Introduction: Breast cancer is the most common cancer in women worldwide, accounting for an estimated 22% of all female cancers. It is the leading cause of cancer mortality in women, almost all of which is due to metastases, with 73% of metastases occurring in the bone. In oncology, metastable technetium 99-labelled methylene bisphosphonate bone scintigraphy (BS) remains the standard examination for detecting and assessing the extent of bone metastases. The aim of this study was to assess the role of BS in the evaluation and follow-up of breast cancer in Senegal. Methodology: This was a retrospective study of breast cancer patients who underwent bone scintigraphy with 99mTc-HMDP in the nuclear medicine department of Idrissa Pouye General Hospital (IPGHO), from July 2009 to June 2022. Results: We enrolled 165 patients, mean age 46.79 years (27 - 87 years). BS was performed in 94.37% of cases for post-therapeutic monitoring and in 5.63% for pre-therapeutic assessment. Results were contributory in 131 patients (92.25%), of whom 72 cases (50.70%) were normal and 59 cases (41.55%) positive or presenting bone metastases;and non-contributory or doubtful in 11 cases (7.75%). Secondary bone locations were multiple in 57 cases (96.61%) and single or solitary in 2 cases (3.39%). The scintigraphic appearance of bone metastases was hyper-fixative in 58 cases (98.31%) and mixed in 1 case (1.69%). Bone lesions were quantified using the Soloway’s grading classification. Conclusion: BS with 99mTc-labelled bisphosphonates remains the examination of choice for skeletal exploration, in the detection and extension of bone metastases in breast cancer. Performance has been enhanced by the development of SPECT coupled with CT (SPECT-CT).

类脂双层(BLM)概念及其实验进展——BLM的40年

类脂双层研究的动力是来自生物世界 .虽然 196 1年首次报道生物体外的双层类脂膜 (BLMs)自组装 ,但从Hooke (16 72年 )起 ,实验科学家一直在处理有关BLM类型的界面吸附现象 .BLMs (或平面的类脂双层 )已应用在许多方面 ,即从基础的膜生物物理学到实际的爱滋病研究 ,从通过水光分解的太阳能转换 ,到应用支持双层类脂膜 (s BLMs)的生物传感器的发展 ,到包括细胞凋亡 (apoptosis)在内的光生物学 .综述了类脂双层概念的起源及其实验进展 ,以及BLMs用作某些生物膜模型的最新研究 .此外 ,简要描述近来有关通过s

Single-atom entropy squeezing and quantum entanglement in Tavis-Cummings model with atomic motion

We examine the single-atom entropy squeezing and the atom-field entanglement in a system of two moving twolevel atoms interacting with a single-mode coherent field in a lossless resonant cavity. Our numerical calculations indicate that the squeezing period, the squeezing time and the maximM squeezing can be controlled by appropriately choosing the atomic motion and the field-mode structure. The atomic motion leads to a periodical time evolution of entanglement between the two-atom and the field. Moreover, there exists corresponding relation between the time evolution properties of the atomic entropy squeezing and that of the entanglement between the two atoms and the field.

Quantum entanglement between the two-mode fields and atomic entropy squeezing in the system of a moving atom interacting with two-mode entangled coherent field

This paper investigates the entropy squeezing of a moving two-level atom interacting with the two-mode entangled coherent field via two-photon transition by using an entropic uncertainty relation and the degree of entanglement between the two-mode fields by using quantum relative entropy.The results obtained from numerical calculation indicate that the squeezed period,the duration of entropy squeezing and the maximal squeezing can be controlled by appropriately choosing the intensity of the light field,the atomic motion and the field-mode structure.The atomic motion leads to the periodic recovery of the initial maximal degree of entanglement between the two-mode fields.Moreover,there exists a corresponding relation between the time evolution properties of the atomic entropy squeezing and those of the entanglement between the two-mode fields.

Suitability of the Composite Made of Multi Wall Carbon Nanotubes-Polyvinylpyrrolidone for Culturing Invertebrate <i>Helix aspersa</i>Neurons

Carbon nanotubes have been used as scaffolds for tissue engineering. However, the identification of these nanomaterials disperses in biological solutions and their direct interaction with nerve cells is still controversial. The aim of this work is to characterize the topographic and ultra-structural distribution of the composite made of multi wall carbon nanotubes-polyvinylpyrrolidone (MWCNTs-PVP) deposited on the Helix aspersa neurons and over glass coverslip. Scanning Electron Microscopy (SEM) and Confocal Microscopy (CM) studies were done to analyze the properties of such MWCNTs-PVP composite. The cerebral ganglion of Helix aspersa was treated and incubated with MWCNTs-PVP, fixing it in paraformaldehyde at 4% and was observed with SEM and CM. Although the nanotubes were not labeled or stained with fluorescent compounds, the MWCNTs-PVP deposited on glass and on nerve cells, was observed by the confocal microscope in the reflection mode. In SEM studies, it was observed that MWCNTs-PVP was attached to the surface on neurons. Moreover, in CM studies, it was possible to observe that MWCNTs-PVP was attached to the neuronal membrane, crossing the cell membrane and getting into the cytoplasm. These results support the hypothesis that carbon nanotubes interact with the neuronal cell membrane and can be useful for neuronal tissue engineering. In addition, these results open new alternatives for toxicological studies, in order to elucidate the cytotoxicity of MWCNTs-PVP composite in neurons and other excitable cells.

Reduced cardiac output is associated with decreased mitochondrial efficiency in the non-ischemic ventricular wall of the acute myocardial-infarcted dog

Cardiogenic shock is the leading cause of death among patients hospitalized with acute myocardial infarction （MI）. Understanding the mechanisms for acute pump failure is therefore important. The aim of this study is to examine in an acute MI dog model whether mitochondrial bio-energetic function within non-ischemic wall regions are associated with pump failure. Anterior MI was produced in dogs via ligation of left anterior descending （LAD） coronary artery, that resulted in an infract size of about 30% of the left ventricular wall. Measurements ofhemodynamic status, mitochondrial function, free radical production and mitochondrial uncoupling protein 3 （UCP3） expression were determined over 24 h period. Hemodynamic measurements revealed a 〉 50% reduction in cardiac output at 24 h post infarction when compared to baseline. Biopsy samples were obtained from the posterior non-ischemic wall during acute infarction. ADP/O ratios for isolated mitochondria from non-ischemic myocardium at 6 h and 24 h were decreased when compared to the ADP/O ratios within the same samples with and without palmitic acid （PA）. GTP inhibition of （PA）-stimulated state 4 respiration in isolated mitochondria from the non-ischemic wall increased by 7% and 33% at 6 h and 24 h post-infarction respectively when compared to sham and pre-infarction samples. This would suggest that the mitochondria are uncoupled and this is supported by an associated increase in UCP3 expression observed on western blots from these same biopsy samples. Blood samples from the coronary sinus measured by electron paramagnetic resonance （EPR） methods showed an increase in reactive oxygen species （ROS） over baseline at 6 h and 24 h post-infarction. In conclusion, mitochondrial bio-energetic ADP/O ratios as a result of acute infarction are abnormal within the non-ischemic wall. Mitochondria appear to be energetically uncoupled and this is associated with declining pump function. Free radical production may be associated with the induction of uncoupling proteins in the mitochondria.

Antihepatoma peptide,scolopentide,derived from the centipede scolopendra subspinipes mutilans

BACKGROUND Centipedes have been used to treat tumors for hundreds of years in China.However,current studies focus on antimicrobial and anticoagulation agents rather than tumors.The molecular identities of antihepatoma bioactive components in centipedes have not yet been extensively investigated.It is a challenge to isolate and characterize the effective components of centipedes due to limited peptide purification technologies for animal-derived medicines.AIM To purify,characterize,and synthesize the bioactive components with the strongest antihepatoma activity from centipedes and determine the antihepatoma mechanism.METHODS An antihepatoma peptide(scolopentide)was isolated and identified from the centipede scolopendra subspinipes mutilans using a combination of enzymatic hydrolysis,a Sephadex G-25 column,and two steps of high-performance liquid chromatography(HPLC).Additionally,the CCK8 assay was used to select the extracted fraction with the strongest antihepatoma activity.The molecular weight of the extracted scolopentide was characterized by quadrupole time of flight mass spectrometry(QTOF MS),and the sequence was matched by using the Mascot search engine.Based on the sequence and molecular weight,scolopentide was synthesized using solid-phase peptide synthesis methods.The synthetic scolopentide was confirmed by MS and HPLC.The antineoplastic effect of extracted scolopentide was confirmed by CCK8 assay and morphological changes again in vitro.The antihepatoma effect of synthetic scolopentide was assessed by the CCK8 assay and Hoechst staining in vitro and tumor volume and tumor weight in vivo.In the tumor xenograft experiments,qualified model mice(male 5-week-old BALB/c nude mice)were randomly divided into 2 groups(n=6):The scolopentide group(0.15 mL/d,via intraperitoneal injection of synthetic scolopentide,500 mg/kg/d)and the vehicle group(0.15 mL/d,via intraperitoneal injection of normal saline).The mice were euthanized by cervical dislocation after 14 d of continuous treatment.Mechanistically,flow cytometry was conducted to evaluate the apoptosis rate of HepG2 cells after treatment with extracted scolopentide in vitro.A Hoechst staining assay was also used to observe apoptosis in HepG2 cells after treatment with synthetic scolopentide in vitro.CCK8 assays and morphological changes were used to compare the cytotoxicity of synthetic scolopentide to liver cancer cells and normal liver cells in vitro.Molecular docking was performed to clarify whether scolopentide tightly bound to death receptor 4(DR4)and DR5.qRT-PCR was used to measure the mRNA expression of DR4,DR5,fas-associated death domain protein(FADD),Caspase-8,Caspase-3,cytochrome c(Cyto-C),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),x-chromosome linked inhibitor-of-apoptosis protein and Cellular fas-associated death domain-like interleukin-1βconverting enzyme inhibitory protein in hepatocarcinoma subcutaneous xenograft tumors from mice.Western blot assays were used to measure the protein expression of DR4,DR5,FADD,Caspase-8,Caspase-3,and Cyto-C in the tumor tissues.The reactive oxygen species(ROS)of tumor tissues were tested.RESULTS In the process of purification,characterization and synthesis of scolopentide,the optimal enzymatic hydrolysis conditions(extract ratio:5.86%,IC_(50):0.310 mg/mL)were as follows:Trypsin at 0.1 g(300 U/g,centipede-trypsin ratio of 20:1),enzymolysis temperature of 46°C,and enzymolysis time of 4 h,which was superior to freeze-thawing with liquid nitrogen(IC_(50):3.07 mg/mL).A peptide with the strongest antihepatoma activity(scolopentide)was further purified through a Sephadex G-25 column(obtained A2)and two steps of HPLC(obtained B5 and C3).The molecular weight of the extracted scolopentide was 1018.997 Da,and the peptide sequence was RAQNHYCK,as characterized by QTOF MS and Mascot.Scolopentide was synthesized in vitro with a qualified molecular weight(1018.8 Da)and purity(98.014%),which was characterized by MS and HPLC.Extracted scolopentide still had an antineoplastic effect in vitro,which inhibited the proliferation of Eca-109(IC_(50):76.27μg/mL),HepG2(IC_(50):22.06μg/mL),and A549(IC_(50):35.13μg/mL)cells,especially HepG2 cells.Synthetic scolopentide inhibited the proliferation of HepG2 cells(treated 6,12,and 24 h)in a concentration-dependent manner in vitro,and the inhibitory effects were the strongest at 12 h(IC_(50):208.11μg/mL).Synthetic scolopentide also inhibited the tumor volume(Vehicle vs Scolopentide,P=0.0003)and weight(Vehicle vs Scolopentide,P=0.0022)in the tumor xenograft experiment.Mechanistically,flow cytometry suggested that the apoptosis ratios of HepG2 cells after treatment with extracted scolopentide were 5.01%(0μg/mL),12.13%(10μg/mL),16.52%(20μg/mL),and 23.20%(40μg/mL).Hoechst staining revealed apoptosis in HepG2 cells after treatment with synthetic scolopentide in vitro.The CCK8 assay and morphological changes indicated that synthetic scolopentide was cytotoxic and was significantly stronger in HepG2 cells than in L02 cells.Molecular docking suggested that scolopentide tightly bound to DR4 and DR5,and the binding free energies were-10.4 kcal/mol and-7.1 kcal/mol,respectively.In subcutaneous xenograft tumors from mice,quantitative real-time polymerase chain reaction and western blotting suggested that scolopentide activated DR4 and DR5 and induced apoptosis in SMMC-7721 Liver cancer cells by promoting the expression of FADD,caspase-8 and caspase-3 through a mitochondria-independent pathway.CONCLUSION Scolopentide,an antihepatoma peptide purified from centipedes,may inspire new antihepatoma agents.Scolopentide activates DR4 and DR5 and induces apoptosis in liver cancer cells through a mitochondria-independent pathway.

Study on the compatibility principle of Wutou Decoction based on network pharmacology

Objective To investigate the underlying drug enhancement mechanisms of the Chuanwu(Aconiti Radix)and Huangqi(Astragali Radix)combination and toxicity reduction of Chuan-wu combined with Gancao(Glycyrrhizae Radix et Rhizoma)in Wutou Decoction(乌头汤,WTD),and to elucidate the compatibility principle.Methods The active compounds and potential effective targets of the selected combinations were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Traditional Chinese Medicines Integrated Database(TCMID).The toxicity of Chuanwu(Aconiti Radix)was investigated by selecting all five toxic compounds from the literature and the TCMSP database,and obtaining their targets through SwissTargetPrediction.Targets related to rheumatoid arthritis(RA)were searched using Dis-GeNET,GenCards,and Online Mendelian Inheritance in Man(OMIM).Mutual targets between the drug pairs and RA were selected as potential RA therapy targets.The medicinally active compound-target network was constructed using Cytoscape 3.9.0.Gene ontology(GO)term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrich-ment were performed using the Database for Annotation,Visualization,and Integrated Dis-covery(DAVID)platform.Results We obtained 191 active compound targets for Gancao(Glycyrrhizae Radix et Rhizoma),171 for Huangqi(Astragali Radix),and 103 for Chuanwu(Radix Aconiti)(hypo-aconitine’s target was obtained through literature and SwissTargetPrediction).A total of 5872 genes were obtained for RA.A drug-active compound-target network involving 13 effect-en-hancing and nine toxicity reduction targets was constructed.PGR was the main effect en-hancement target,and KCNH2 was the main toxicity reduction target.The effect-enhancing targets were related to 23 GO terms(such as positive regulation of transcription from RNA polymerase II promoter,steroid hormone-mediated signaling pathway,plasma membrane,and protein binding)(P<0.01),and 13 KEGG pathways related to synergism[such as estro-gen signaling pathway,cholinergic synapse,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway].The toxicity reduction targets were related to 28 GO terms(mainly involes G-protein coupled receptor signaling pathway,plasma membrane,and drug binding)(P<0.01),and five KEGG pathways related to toxicity reduction(cholinergic syn-apse,calcium signaling pathway,regulation of actin cytoskeleton,neuroactive ligand-recept-or interaction,and serotonergic synapse).Conclusion The combination of Chuanwu(Aconiti Radix)and Huangqi(Astragali Radix)plays an important effect-enhancing role in WTD and involves the estrogen and PI3K/Akt sig-naling pathways,with PGR as the core.The Chuanwu(Aconiti Radix)and Gancao(Gly-cyrrhizae Radix et Rhizoma)combination decreases toxicity in WTD and is associated with the cholinergic synapse and calcium signaling pathways,with KCNH2 as the core.

Recording potentials from scala media, saccule and utricle in mice

Objective： To describe a protocol for recording electrical potentials from the scala media, saccule, and utricle in mice. Method： CBA/J mice were used and potentials were recorded with glass electrodes inserted through the basilar membrane using a patch clamp system. Results： Resting potentials were successfully recorded from the scala media, saccule and utricle using described protocols. Conclusions： With the method described, one can measure resting potentials from the scala media, saccule and utricle, as well as cochlear microphonics （CM） and even auditory nerve compound action potentials （CAP）, in a single mouse.

Antitumor Effect of Cationic INKKI Peptide from Bovine <i>β</i>-Casein on Melanoma B16F10

Cationic peptide with the sequence INKKI 41-45 was isolated from bovine β-casein after tryptic hydrolysis and synthetized. The aim of this work was to evaluate the antiproliferative activity in vitro and antitumor effect in animal model. The in vitro cytotoxicity was evaluated on B16F10 melanoma cells by MTT assay. Detection of apoptosis was measured using the annexin V/PI double staining and cell cycle analysis performed flow cytometry. Caspase-3 activity was analyzed with substrate specific fluorogenic DEVD-MCA. In vivo, antitumor activity was evaluated in B16F10 melanoma tumor-bearing C57BL/6J mice. The animals were treated with 55 mg/kg INKKI administered into peritumoral region, while control group received saline solution. The following antitumor parameters were examined: tumor volume, number of metastases, tumor delayed time, tumor doubling time. Histological analyses were performed with H & E staining. The results showed that INKKI induced dose-response cytotoxicity selective for B16F10 melanoma cells (IC50 1.7 μM) and did not present cytotoxic effects for FN1 fibroblast cells. INKKI-induced apoptosis detected trough of annexin V/PI assay and it was accompanied with an increase of sub-G1 apoptotic fractions and significant increase of caspase-3 cleavage. The tumor-bearing mice treated with INKKI showed a significant reduction in tumor volume of 72.62% and decreased of metastasis number loci. In addition, INKKI caused a significant delay in tumor growth and prolonged the tumor doubling time. Histological analysis revealed an increased of necrosis areas and reduction of tumor cells in tumor treated with INKKI, it was a many hallmark of its antitumor effects observed from in vivo experiments. In conclusion, we show that INKKI is a peptide that could be considered a new putative candidate development to anticancer therapy drug.

Annual Committed Effective Dose from Various Phytotherapeutic Preparations (due to 238U, 232Th, 222Rn and 220Rn) Estimated for Adult Moroccan Patients

We use a nuclear technique based on the determination of the detection efficiencies of solid state nuclear track detectors CR-39 and LR-115 type II (SSNTDs) for alpha particles emitted from the series of uranium-238 and thorium-232 in a phytotherapeutic sample and the measurement of alpha track densities registered on these detectors to assess alpha activities due to uranium-238;thorium-232;radon and thoron in samples of phytotherapeutic preparations consumed by Moroccan adult patients. For modern preparations, the alpha activities due to 238U, 232Th and 222Rn range from 14.27 mBq/kg to 22.02 mBq/kg, from 6.27 mBq/kg to 9.64 mBq/kg and from 14.27 Bq/kg to 22.02 Bq/kg respectively. For classical preparations, the alpha activities due to 238U, 232Th and 222Rn range from 16.73 mBq/kg to 24 mBq/kg, from 7.34 mBq/kg to 10.82 mBq/kg and from 16.73 Bq/kg to 24.72 Bq/kg respectively. A dosimetric model for ingestion has been highlighted to determine committed equivalent dose to different compartments of human gastrointestinal system due to the ingestion of phytotherapeutic preparations by Moroccan adult patients. The maximum overall effective dose due to 238U, 232Th, and 222Rn after the ingestion of the studied phytotherapeutic preparations, was found equal to 38 × 10-8 S·vy-1 which is less than the dose limit given by the international commission for radiological protection in it publication 56.

A robust luminescent assay for screening alkyladenine DNA glycosylase inhibitors to overcome DNA repair and temozolomide drug resistance

Temozolomide(TMZ)is an anticancer agent used to treat glioblastoma,typically following radiation therapy and/or surgical resection.However,despite its effectiveness,at least 50%of patients do not respond to TMZ,which is associated with repair and/or tolerance of TMZ-induced DNA lesions.Studies have demonstrated that alkyladenine DNA glycosylase(AAG),an enzyme that triggers the base excision repair(BER)pathway by excising TMZ-induced N3-methyladenine(3meA)and N7-methylguanine lesions,is overexpressed in glioblastoma tissues compared to normal tissues.Therefore,it is essential to develop a rapid and efficient screening method for AAG inhibitors to overcome TMZ resistance in glioblastomas.Herein,we report a robust time-resolved photoluminescence platform for identifying AAG inhibitors with improved sensitivity compared to conventional steady-state spectroscopic methods.As a proof-of-concept,this assay was used to screen 1440 food and drug administration-approved drugs against AAG,resulting in the repurposing of sunitinib as a potential AAG inhibitor.Sunitinib restored glioblastoma(GBM)cancer cell sensitivity to TMZ,inhibited GBM cell proliferation and stem cell characteristics,and induced GBM cell cycle arrest.Overall,this strategy offers a new method for the rapid identification of small-molecule inhibitors of BER enzyme activities that can prevent false negatives due to a fluorescent background.

A Novel 3-D Nano-assembly Bacteria Based Biosensor for Enhanced Detection of Heavy Metal Pollutants

Nowadays, at a time of growing concern for sustainable development and compliance with environmental standards and legislation, the detection of heavy metal contaminants in environmental matrices represents a difficult but important task. The current major limitation lies in the poor detection limits of the targeted pollutant＇s trace concentrations by the available conventional techniques. In order to elaborate a novel ＂living＂ self assembled electrochemical 3-D biosensor, the authors propose a new concept to overcome this shortcoming. The advantages of the properties of polyelectrolyte-functionalized NBs （nanobeads） are combined along with the use of non covalently strongly bound micro-organisms. The designed 3-D biosensor is all the more promising as it has showed a significantly improved sensitivity. In fact, the detection limits of the tested heavy metals （cadmium and mercury） were as low as 1.0 × 10^-12 mol.L-1 and six to seven orders of magnitude lower than those provided by conventional 2-D biosensors. Furthermore, it is potentially applicable to a wide range of bioreceptor-pollutant detection systems.