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Push forward LC-MS-based therapeutic drug monitoring and pharmacometabolomics for anti-tuberculosis precision dosing and comprehensive clinical management

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Journal of Pharmaceutical Analysis 2024年第1期14卷 16-38页

作者： Nguyen Quang Thu Nguyen Tran Nam Tien Nguyen Thi Hai Yen Thuc-Huy Duong Nguyen Phuoc Long Huy Truong Nguyen department of pharmacology and PharmacoGenomics Research Center Inje University College of MedicineBusan47392Republic of Korea department of Chemistry University of EducationHo Chi Minh City700000Viet Nam Faculty of Pharmacy Ton Duc Thang UniversityHo Chi Minh City700000Viet Nam

The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB *** strategies to facilitate drug combinations,including pharmacokinetics-guided dose optimization and toxicology studies of first-and second-line anti-TB drugs have also been introduced and *** chromatography-mass spectrometry(LC-MS)has arguably become the gold standard in the analysis of both endo-and exo-genous *** technique has been applied successfully not only for therapeutic drug monitoring(TDM)but also for pharmacometabolomics *** improves the effectiveness of treatment,reduces adverse drug reactions,and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target *** on TDM,the dose would be optimized individually to achieve favorable *** is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs,aiding in the discovery of potential biomarkers for TB diagnostics,treatment monitoring,and outcome *** article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two ***,we discussed the advantages and disadvantages of this technique in practical *** pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was ***,we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies(pharmacometrics,drug and vaccine developments,machine learning/artificial intelligence,among others)to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.

关键词： Tuberculosis Therapeutic drug monitoring LC-MS MIPD Pharmacometabolomics Precision medicine

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Impact of carbimazole combined with vitamin E on testicular injury induced by experimental hyperthyroidism in adult albino rats:oxidative/inflammatory/apoptotic pathways

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Asian Journal of Andrology 2024年第4期26卷 396-401页

作者： Ramadan S Hussein Moustafa M Eyada Rashad M Mostafa Samah M Elaidy Shereen H Elsayed Hany M Saad department of Dermatology College of Medicine Prince Sattam Bin Abdulaziz UniversityAl-Kharj 16242Saudi Arabia department of Dermatology Andrology and STDsAssiut Police HospitalAssiut 71525Egypt department of Dermatology Venereology and AndrologyFaculty of MedicineSuez Canal UniversityIsmailia 41522Egypt department of Andrology and Sexology Faculty of MedicineSuez Canal UniversityIsmailia 41511Egypt department of clinical pharmacology Faculty of MedicineSuez Canal UniversityIsmailia 41511Egypt department of Rehabilitation Sciences Faculty of Health and Rehabilitation SciencesPrincess Nourah bint Abdulrahman UniversityRiyadh 12271Saudi Arabia.

Thyroid hormones play essential roles in spermatogenesis,but their effects on infertile males remain poorly *** study aimed to evaluate the impact of combining carbimazole(CBZ)with vitamin E(VE)on testicular injury induced by experimental hyperthyroidism in adult albino rats,focusing on oxidative,inflammatory,and apoptotic *** this experimental study,64 adult male albino Wistar rats were divided into eight groups:Group I(control-untreated),Group II(CBZ-control),Group III(VE-control),Group IV(CBZ+VE-control),Group V(levothyroxine-induced testicular injury),Group VI(levothyroxine+CBZ-treated),Group VII(levothyroxine+VE-treated),and Group VIII(levothyroxine+CBZ+VE-treated).The study was conducted in the Faculty of Medicine,Suez Canal University(Ismailia,Egypt).After cervical decapitation,both testes and epididymis were examined histopathologically and *** differences were observed among groups concerning malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD),and catalase(CAT;all P<0.001).Polymerase chain reaction analysis showed significant differences in tumor necrosis factor-α(TNF-α),interleukin-10(IL-10),Bcl-2-associated X protein(BAX),B-cell lymphoma 2 protein(Bcl2),p53,Caspase-3,Caspase-8,Caspase-9,and nuclear factor-kappa B(NF-κB)mRNA levels(all P<0.001).Hyperthyroid group treated with CBZ alone(Group VI)exhibited testicular side effects,affecting seminiferous tubules and ***,the Group VIII showed improved spermatogenesis and a decrease in testicular side *** addition of VE to the treatment of hyperthyroid rats with CBZ reduced testicular side effects and seminiferous tubular affection when potentially improving *** research is needed to elucidate the underlying mechanisms fully.

关键词： antithyroid drugs testicular injury thyroid gland vitamin E

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Transferrin receptor-targeted immunostimulant for photodynamic immunotherapy against metastatic tumors through b-catenin/CREB interruption

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4118-4133页

作者： Mengyi Yan Xiayun Chen Xiaotong Li Qianqian Liu Baixue Yu Yi Cen Wei Zhang Yibin Liu Xinxuan Li Ying Chen Tao Wang Shiying Li The Fifth Affiliated Hospital Guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacologythe NMPA and State Key Laboratory of Respiratory Diseasethe School of Pharmaceutical SciencesGuangzhou Medical UniversityGuangzhou 511436China department of Anesthesiology the Second Clinical School of Guangzhou Medical UniversityGuangzhou 511436China State Key Laboratory of Respiratory Diseases Guangdong Key Laboratory of Vascular DiseasesGuangzhou Institute of Respiratory Healththe first Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510120China department of Pulmonary and Critical Care Medicine Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China

The immunosuppressive phenotype of tumor cells extensively attenuates the immune activation effects of traditional *** this work,a transferrin receptor(TfR)targeted immunostimulant(PTI)is fabricated for photodynamic immunotherapy against metastatic tumors by interrupting b-catenin signal *** synthesize PTI,the photosensitizer conjugated TfR targeting peptide moiety(Palmitic-K(PpIX)-HAIYPRH)is unitized to encapsulate the transcription interrupter of *** the one hand,the recognition of PTI and TfR can promote drug delivery into tumor cells to destruct primary tumors through photodynamic therapy and initiate an immunogenic cell death with the release of tumorassociated *** the other hand,PTI will interrupt the binding between b-catenin andcAMP response element-binding protein(CREB),regulating the gene transcription to downregulate programmed death ligand 1(PD-L1)while upregulating CeC motif chemokine ligand 4(CCL4).Furthermore,the elevated CCL4 can recruit the dendritic cells to present tumor-specific antigens and promote T cells activation and infiltration,and the downregulated PD-L1 can avoid the immune evasion of tumor cells and activate systemic anti-tumor immunity to eradicate lung *** work may inspire the development of antibody antibody-free strategy to activate systemic immune response in consideration of immunosuppressive conditions.

关键词： Transferrin receptor b-Catenin signal pathway Tumor targeting Photodynamic therapy Immunotherapy Immunogenic cell death Programmed death ligand 1

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Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong Miao Michael S.Wolfe Computational Medicine Program and department of pharmacology University of North Carolina–Chapel HillChapel HillNCUSA department of Medicinal Chemistry University of KansasLawrenceKSUSA

γ-Secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-Secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-Stay-Trim,”“Sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

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Understanding the Novel Approach of Nanoferroptosis for Cancer Therapy

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Nano-Micro Letters 2024年第9期16卷 501-556页

作者： Afsana Sheikh Prashant Kesharwani Waleed H.Almalki Salem Salman Almujri Linxin Dai Zhe‑Sheng Chen Amirhossein Sahebkar Fei Gao department of Pharmaceutics School of Pharmaceutical Education and ResearchJamia HamdardNew Delhi 110062India department of pharmacology and Toxicology Faculty of PharmacyUmm Al-Qura UniversityMakkahSaudi Arabia department of pharmacology College of PharmacyKing Khalid University61421 Asir‑AbhaSaudi Arabia State Key Laboratory of Southwestern Chinese Medicine Resources Pharmacy SchoolChengdu University of Traditional Chinese MedicineChengdu 611130People’s Republic of China department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityNew York 11439USA Biotechnology Research Center Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran Applied Biomedical Research Center Mashhad University of Medical SciencesMashhadIran

As a new form of regulated cell death,ferroptosis has unraveled the unsolicited theory of intrinsic apoptosis resistance by cancer *** molecular mechanism of ferroptosis depends on the induction of oxidative stress through excessive reactive oxygen species accumulation and glutathione depletion to damage the structural integrity of *** to their high loading and structural tunability,nanocarriers can escort the delivery of ferro-therapeutics to the desired site through enhanced permeation or retention effect or by active *** review shed light on the necessity of iron in cancer cell growth and the fascinating features of ferroptosis in regulating the cell cycle and ***,we discussed the effect of ferroptosis-mediated therapy using nanoplatforms and their chemical basis in overcoming the barriers to cancer therapy.

关键词： Ferroptosis Nanoparticles Ferrotherapy Cancer Genes Nanotechnology Toxicity Reactive oxygen species

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Context-dependent role of sirtuin 2 in inflammation

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Neural Regeneration Research 2025年第3期20卷 682-694页

作者： NoemíSola-Sevilla Maider Garmendia-Berges MCarmen Mera-Delgado Elena Puerta department of Pharmaceutical Sciences Division of PharmacologySchool of Pharmacy and NutritionUniversity of NavarraPamplonaSpain Navarra Institute for Health Research(IdiSNA) PamplonaSpain

Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.

关键词： interferon inflammation lipopolysaccharide neuroinflammation NLRP3 nuclear factorκB sirtuin 2

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A comparative in vitro study on the effect of SGLT2 inhibitors on chemosensitivity to doxorubicin in MCF-7 breast cancer cells

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Oncology Research 2024年第5期32卷 817-830页

作者： SHAHID KARIM ALANOUD NAHER ALGHANMI MAHA JAMAL HUDA ALKREATHY ALAM JAMAL HIND A.ALKHATABI MOHAMMED BAZUHAIR AFTAB AHMAD department of clinical pharmacology Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia department of Biochemistry Faculty of ScienceKing Abdulaziz UniversityJeddahSaudi Arabia department of Biochemistry College of ScienceUniversity of JeddahJeddah21959Saudi Arabia Health Information Technology department The Applied CollegeKing Abdulaziz UniversityJeddahSaudi Arabia Pharmacovigilance and Medication Safety Unit Center of Research Excellence for Drug Research and Pharmaceutical IndustriesKing Abdulaziz UniversityJeddahSaudi Arabia

Cancer frequently develops resistance to the majority of chemotherapy *** study aimed to examine the synergistic cytotoxic and antitumor effects of SGLT2 inhibitors,specifically Canagliflozin(CAN),Dapagliflozin(DAP),Empagliflozin(EMP),and Doxorubicin(DOX),using in vitro *** precise combination of CAN+DOX has been found to greatly enhance the cytotoxic effects of doxorubicin(DOX)in MCF-7 ***,it was shown that cancer cells exhibit an increased demand for glucose and ATP in order to support their ***,when these medications were combined with DOX,there was a considerable inhibition of glucose consumption,as well as reductions in intracellular ATP and lactate ***,this effect was found to be dependent on the dosages of the *** addition to effectively inhibiting the cell cycle,the combination of CAN+DOX induces substantial modifications in both cell cycle and apoptotic gene *** work represents the initial report on the beneficial impact of SGLT2 inhibitor medications,namely CAN,DAP,and EMP,on the responsiveness to the anticancer properties of *** underlying molecular mechanisms potentially involve the suppression of the function of SGLT2.

关键词： SGLT2 Cancer Cytotoxicity ATP Cell cycle

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Efficacy of intraovarian autologous platelet-rich plasma administration in women with low ovarian reserve: A systematic review and meta-analysis

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Asian pacific Journal of Reproduction 2024年第2期13卷 60-67页

作者： Yasmin Sabina Sa’diah Agung Dewanto Lukman A Chandra department of Obstetrics and Gynecology Faculty of MedicinePublic Health and NursingUniversitas Gadjah MadaYogyakartaIndonesia department of pharmacology and Therapy Faculty of MedicinePublic Health and NursingUniversitas Gadjah MadaYogyakartaIndonesia

Objective:To conduct a systematic examination and meta-analysis of the most reliable data from experimental studies evaluating the efficacy of autologous platelet-rich plasma(PRP)on low ovarian ***:A comprehensive search was performed utilizing pertinent search terms across electronic databases,including PubMed,Cochrane,and Google *** included studies that assigned infertile women with low ovarian reserve in experimental *** reserve parameters were measured before and after PRP injection into *** data of each study was retrieved and subsequently ***:Of 301 articles collected and reviewed,six studies were finally included in the *** PRP injection,infertile women showed a non-significant increase in anti-Mullerian hormone(AMH)level(MD=0.10;95%CI-0.04,0.23),a significant increase in antral follicular count(AFC)(MD=1.88;95%CI 0.47,3.29),and a non-significant reduction in follicle-stimulating hormone(FSH)level(MD=-0.22;95%CI-8.32,7.87).Conclusions:Autologous PRP may increase AFC,but not *** it is found beneficial in enhancing ovarian reserve(AFC),further research with strong evidence is still required.

关键词： Platelet-rich plasma Low ovarian reserve Ovarian rejuvenation

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Corneal and intraocular pressure changes associated to the circadian rhythms:a narrative review

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International Journal of Ophthalmology(English edition) 2024年第10期17卷 1921-1928页

作者： Laura Barberán-Bernardos MiguelÁngel Ariza-Gracia David P Piñero department of Optics Pharmacology and AnatomyUniversity of AlicanteSan Vicente del Raspeig 03690AlicanteSpain ARTORG Center for Biomedical Engineering Research University of BernBern 3008Switzerland department of Ophthalmology(IMQO-Oftalmar) Vithas Medimar International HospitalAlicante 03016Spain

AIM:To synthesize the current body of research regarding the diurnal variations in intraocular pressure(IOP)and corneal biomechanical and morphological parameters,highlighting their significance in various eye ***:A comprehensive review of studies on the diurnal variations of IOP and corneal parameters was *** findings from various studies were assessed,including the Goldmann applanation tonometry(GAT)and non-contact *** on the variations in central corneal thickness(CCT),corneal curvature,and corneal biomechanics measured by the Ocular Response Analyzer system across different population groups was extracted and ***:In both healthy subjects and those with Fuchs dystrophy,IOP and CCT demonstrate marked diurnal *** remains the gold standard for tonometry,with the highest ***,its measurements are influenced by *** patients and those with pseudoexfoliation showed significant diurnal variations in *** biomechanical parameters,especially corneal hysteresis(CH)and the corneal resistance factor(CRF),largely remain stable throughout the day for most of eye conditions,with some ***,the corneal morphology diurnal variation,particularly curvature,yielded mixed conclusions across ***:Circadian rhythms significantly influence various corneal parameters,most notably IOP and *** studies should emphasize standardized approaches larger sample sizes,and delve deeper into less-explored areas,such as the effects of orthokeratology lenses on diurnal biomechanical shifts.

关键词： circadian rhythms intraocular pressure corneal thickness corneal biomechanics corneal curvature

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Site-specific incorporation of reduction-controlled guest amino acids into proteins for cucurbituril recognition

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Chinese Chemical Letters 2024年第5期35卷 193-196页

作者： Zhen Dai Linzhi Tan Yeyu Su Kerui Zhao Yushun Tian Yu Liu Tao Liu College of Chemistry State Key Laboratory of Elemento-Organic ChemistryNankai UniversityTianjin 300071China State Key Laboratory of Natural and Biomimetic Drugs Department of Molecular and Cellular PharmacologySchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China

Protein recognition using host-guest recognition approach is of great interest but has been limited mainly to the protein N-terminal ***,we site-specific incorporated two novel non-canonical amino acids containing supramolecular guest motifs into protein via an expanded genetic *** Staudinger reduction reactions,the encoded unnatural residues on protein becoming activated and can be specifically recognized by cucurbit[7]uril(CB[7])and cucurbit[8]uril(CB[8]).We demonstrated that enzyme containing guest amino acid incorporated near the active site can be reversibly regulated by CB[7]recognition,and CB[8]recognition induces protein *** amino acids will make useful addition to the supramolecular toolbox for protein targeting using molecular recognition approaches.

关键词： Protein recognition Host-guest recognition Non-canonical amino acids Staudinger reduction Expanded genetic code

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