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Formulation strategies in immunotherapeutic pharmaceutical products

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World Journal of Clinical oncology 2020年第5期11卷 275-282页

作者： Yajie Zhang robert o williams ⅲ Haley oana Tucker Division of Molecular Pharmaceutics and Drug Delivery College of PharmacyThe University of Texas at AustinAustinTX 78712United States Departments of Bioengineering and Molecular Biosciences The University of Texas at AustinAustinTX 78712United States

Development of immunologic-based biopharmaceutical products have strikingly increased in recent years and have made evident contributions to human *** are the leading entity in immunotherapy,while chimeric antigen receptor T cells therapies are the advent of a novel strategy in this *** order to enable antibody candidates or cells available as products,formulation is critical in terms of stabilize molecules or cells to achieve practical shelf life,storage and handling *** we provide a concise and contemporary review of ongoing formulation strategies and excipients used in approved antibodies and cellular therapeutic *** are categorized,and their function in formulations are discussed.

关键词： Immunotherapeutic Pharmaceutical products Formulation Excipients Cell therapy Antibody

Three-stage pyrolysis–steam reforming–water gas shift processing of household,commercial and industrial waste plastics for hydrogen production

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Waste Disposal and Sustainable Energy 2024年第1期6卷 25-37页

作者： Rayed Alshareef robert Sait-Stewart Mohamad A.Nahil Paul T.williams School of Chemical and Process Engineering University of LeedsLeedsLS29JTUK

Five common single plastics and nine different household,commercial and industrial waste plastics were processed using a three-stage(i)pyrolysis,(ii)catalytic steam reforming and(iii)water gas shift reaction system to produce *** of plastics produces a range of different hydrocarbon species which are subsequently catalytically steam reformed to produce H_(2)and Co and then undergo water gas shift reaction to produce further H_(2).The process mimics the commercial process for hydrogen production from natural *** of the single polyalkene plastics(high-density polyethylene(HDPE),low-density polyethylene(LDPE),and polypropylene(PP))produced similar H_(2)yields between 115 mmol and 120 mmol per gram *** though PS produced an aromatic product slate from the pyrolysis stage,further stages of reforming and water gas shift reaction produced a gas yield and composition similar to that of the polyalkene plastics(115 mmol H_(2)per gram plastic).PET gave significantly lower H_(2)yield(41 mmol per gram plastic)due to the formation of mainly Co,Co_(2)and organic acids from the pyrolysis stage which were not conducive to further reforming and water gas shift reaction.A mixture of the single plastics typical of that found in municipal solid waste produced a H_(2)yield of 102 mmol per gram *** the gas yields and composition from the single plastics enabled an estimation of the yields from a simulated waste plastic mixture and a‘real-world’waste plastic mixture to be *** different household,commercial and industrial waste plastic mixtures produced H_(2)yields between 70 mmol and 107 mmol per gram *** H_(2)yield and gas composition from the single waste plastics gave an indication of the type of plastics in the mixed waste plastic samples.

关键词： Waste plastic Hydrogen Catalyst Pyrolysis reforming Water gas shift

Nucleotide Contribution to the Functioning of SERT, Na/K ATPase and GPCR Proteins

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Journal of Biosciences and Medicines 2024年第5期12卷 61-76页

作者： Wynford robert williams Faculty of Life Sciences & Education University of South Wales Cardiff UK

Purine nucleotides are crucial for the effective operation of cell membrane proteins maintaining the neurotransmitter responses of 5-HT. Major protein targets in the treatment of depression include SERT, N/K ATPase and GPCR. Each protein target is responsive to a specific complement of drugs: antidepressants (SERT), lithium and cardiogenic steroids (N/K ATPase), 5-HT receptor ligands (GPCR). Computational software is useful for comparing molecular similarity within ligand-ligand and ligand-nucleotide structures. Previous studies demonstrate that GPCR ligands of different pharmacologic classes display relative molecular similarity to nucleotide structures. The current study applies this methodology to compound structures modulating SERT and N/K ATPase receptors. Minimum energy conformers of SERT antagonists demonstrate relative molecular similarity to the structural template of GTP nucleotide. GTP template fits of 5-HT and psilocin are similar, whereas a SERT-like fit is one of several for the ketamine structure. Endogenous and pharmaceutical modulators of Na/K ATPase relate to adenine nucleotide. The fits of cardiogenic steroids to a cGMP template demonstrate similarities and differences between compounds. Relative molecular similarity within the structures of hormones, drugs and nucleotides has implications for neurotransmitter transport and cell signal transduction processes.

关键词： SERT SSRI GPCR Sodium/Potassium ATPase Nucleotides Depression

水难溶性药物制剂的设计——选择正确的方式（英文）

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水难溶性药物制剂的设计——选择正确的方式（英文）

Sickle cell retinopathy and systemic disease

2018年第十二届中国药物制剂大会

作者： robert o.williams 德克萨斯大学奥斯汀分校

Processes including spray-drying, hot melt extrusion and KinetiSol? Dispersing, are useful processes for formulating poorly water soluble drugs in order to improve their properties, such as wetting, dissolution and bioavailability. Polymers are typically employed in these processes to formulate the drug as an amorphous solid dispersion. Spray-drying requires that the drug is soluble in a suitable organic solvent. Thermally labile drugs and drugs that have a high melting point（e.g., greater than 200 ℃） are often not suitable to be processed using hot melt extrusion. KinetiSol? Dispersing, a high energy fusion process not requiring an external heat source, offers a suitable alternative to these difficult to formulate drugs. Processing considerations differ in terms of such parameters as processing time and stability to heat and shear. This talk will compare and contrast formulation considerations involved in process selection to make amorphous solid dispersions, and will include examples of formulations and processes showing enhanced properties.

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Annals of Eye Science 2024年第2期9卷 53-61页

作者： oladipupo o.Anibire Daniel ABrill Basil K.williams Jr Meharry Medical College NashvilleTNUSA Department of ophthalmology University of Cincinnati College of MedicineCincinnatiOHUSA Cincinnati Eye Institute CincinnatiOHUSA Bascom Palmer Eye Institute University of Miami Miller School of MedicineMiamiFLUSA

Sickle cell disease(SCD)is a widespread hemoglobinopathy that results in significant patient morbidity and *** occlusion can cause acute pain,acute chest syndrome,and avascular necrosis,while hemolysis and endothelial disruption can cause ischemic stroke,leg ulcers,pulmonary hypertension,and *** ocular and orbital structures can be affected by SCD ischemic events,including orbital bone infarction,ischemic optic neuropathy,retinal artery occlusion,hyphema,secondary glaucoma,sickle cell maculopathy,and sickle cell *** sickle cell retinopathy(PSR)is the most common cause of vision *** PSR can lead to macular ischemia,vitreous hemorrhage,and tractional retinal *** screening exams and multimodal imaging can lead to earlier detection of sickle cell retinopathy and improved patient *** patients undergoing vitreoretinal surgery may require coordination of care with hematologists to avoid ischemic *** hydroxyurea was the only United States Food and Drug Administration approved treatment for several decades,patients with SCD now have several more treatment *** the United States screening all infants for SCD,there can be delays in diagnosis and *** review article aims to provide an overview of sickle disease for the ophthalmologist,and to discuss emerging treatment options and current management of SCD ocular complications.

关键词： Sickle cell anemia sickle cell disease(SCD) sickle cell retinopathy retinal detachment vitreous hemorrhage(VH)

Surgeon preferences in the treatment of thumb carpometacarpal osteoarthritis

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World Journal of orthopedics 2024年第5期15卷 435-443页

作者： Edward J Wu Bradley W Fossum Wyatt Vander Voort Christopher o Bayne robert M Szabo Department of orthopedic Surgery University of Minnesota Medical SchoolMinneapolisMN 55455United States Department of orthopaedic Surgery UC Davis School of MedicineSacramentoCA 95817United States

BACKGRoUND Primary thumb carpometacarpal(CMC)osteoarthritis is one of the most common conditions encountered by hand *** the vast number of operations that have been proposed,none have demonstrated results significantly superior to trapeziectomy *** The purpose of our study was to determine why surgeons opt for their technique in treating CMC *** A cross-sectional survey of active members of the American Society for Surgery of the Hand was conducted to evaluate the reasons behind their preferred technique in the treatment of isolated thumb CMC *** were contacted by email once and provided with a link to a de-identified survey consisting of 5 treatment questions and 5 demographic *** of 950 responses were received.40.5%of surgeons preferred trapeziectomy+ligament reconstruction tendon interposition(LRTI),followed by trapeziectomy+suspensionplasty(28.2%),suture button suspension(5.9%),trapeziectomy alone(4.6%),prosthetic arthroplasty(3.2%),arthrodesis(1.1%),and other(6.6%).Proponents of trapeziectomy+LRTI cited familiarity(73.2%),exposure during fellowship(48.8%)and less proximal migration(60%)to be the main reasons affecting their *** who preferred trapeziectomy+suspensionplasty most reported simplicity(74.9%),fewer complications(45.3%),less proximal migration(43.8%),and avoidance of autogenous tissue harvest(42.7%).Advocates of suture button suspension cited avoidance of autogenous tissue harvest(80.4%),shorter immobilization(76.8%),and quicker recovery(73.2%)with their *** of trapeziectomy alone cited simplicity(97.7%),fewer complications(86.4%),and avoidance of autogenous tissue harvest(59.1%).In their comments,45%of surgeons choosing trapeziectomy alone cited evidence as an additional *** of prosthetic arthroplasty cited improved pinch strength(83.3%)and improved range of motion(63.3%),while those preferring arthrodesis cited better pinch strength(90%)and freque

关键词： Thumb carpometacarpal osteoarthritis Trapeziectomy Ligament reconstruction tendon interposition Suspensionplasty Preferences Trends

outcomes of endoscopic submucosal dissection in cirrhotic patients: First American cohort

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World Journal of Hepatology 2024年第5期16卷 784-790页

作者： robert Luke Pecha Fares Ayoub Ankur Patel Abdullah Muftah Michael W Wright Mai A Khalaf Mohamed o othman Department of Gastroenterology and Hepatology UC DavisSacramentoCA 95817United States Department of Gastroenterology and Hepatology Baylor College of MedicineHoustonTX 77030United States Internal Medicine Baylor College of MedicineHoustonTX 77030United States Department of Gastroenterology and Hepatology University of Texas Medical Branch at GalvestonGalvestonTX 77550United States Medical School Baylor College of MedicineHoustonTX 77030United States Department of Tropical Medicine Tanta UniversityTanta 31527Egypt

BACKGRoUND Among patients with cirrhosis and pre-malignant or early malignant mucosal lesions,surgical intervention carries a much higher bleeding *** such lesions are discovered,endoscopic submucosal dissection(ESD)may offer curative therapy with lower risks than surgery and improved outcomes compared to traditional endoscopic *** To evaluate the outcomes of ESD in patients with *** Patients with cirrhosis undergoing ESD between July 2015 and August 2022 were retrospectively matched in 1:2 fashion to controls based on lesion location,size,and anticoagulation *** outcomes were compared between *** A total of 64 Lesions from 59 patients were included(16 cirrhosis,43 control).There were no differences in patient or lesion characteristics between *** bloc and curative resection was achieved in 84.21%,78.94%of the cirrhosis group and 88.89%,68.89%of controls,respectively,with no significant *** patients had significantly higher rates of intra-procedural coagulation grasper use for control of bleeding(47.37%vs 20%;P=0.02).There were otherwise no significant differences in adverse event *** the 29 patients with follow up,we found higher rates of recurrence in the cirrhosis group compared to controls(40%vs 5.26%;P=0.019),however this effect did not persist on multivariable analysis controlling for known *** ESD may be safe and effective in patients with *** procedure related outcomes were not significantly different between ***-procedural bleeding requiring use of the coagulation grasper use was expectedly higher in the cirrhosis group given the known effects of liver disease on hemostasis.

关键词： Endoscopic aubmucosal dissection Cirrhosis Advanced polypectomy Intraprocedural bleeding Colon cancer

The concept of gene therapy for glaucoma:the dream that has not come true yet

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Neural Regeneration Research 2024年第1期19卷 92-99页

作者： robert Sulak Xiaonan Liu Adrian Smedowski Department of Physiology Faculty of Medical Sciences in KatowiceMedical University of Silesia in KatowiceKatowicePoland Institute of Biotechnology HiLIFEUniversity of HelsinkiHelsinkiFinland GlaucoTech Co. KatowicePoland

Gene therapies,despite of being a relatively new therapeutic approach,have a potential to become an important alternative to current treatment strategies in *** glaucoma is not considered a single gene disease,the identified goals of gene therapy would be rather to provide neuroprotection of retinal ganglion cells,especially,in intraocular-pressure-independent *** most commonly reported type of vector for gene delivery in glaucoma studies is adeno-associated virus serotype 2 that has a high tro pism to retinal ganglion cells,res ulting in long-term expression and low immunogenic *** gene thera py studies recruit inducible and genetic animal models of optic neuropathy,like DBA/2J mice model of high-tension glaucoma and the optic nerve *** gene therapy-based neuroprotection of retinal ganglion cells is targeting specific genes translating to growth factors(i.e.,brain derived neurotrophic factor,and its receptor TrkB),regulation of apoptosis and neurodegeneration(i.e.,Bcl-xl,Xiap,FAS system,nicotinamide mononucleotide adenylyl transferase 2,Digit3 and Sarm1),immunomodulation(i.e.,Crry,C3 complement),modulation of neuroinflammation(i.e.,e rythropoietin),reduction of excitotoxicity(i.e.,Com KIlα)and transcription regulation(i.e.,Max,Nrf2).on the other hand,some of gene therapy studies focus on lowering intra ocular pressure,by impacting genes involved in both,decreasing aqueous humor production(i.e.,aquaporin 1),and increasing outflow facility(i.e.,CoX2,prostaglandin F2a receptor,RhoA/RhoA kinase signaling pathway,MMP1,Myocilin).The goal of this review is to summarize the current stateof-art and the direction of development of gene therapy strategies for glaucomatous neuropathy.

关键词： adeno-associated virus gene editing gene therapy glaucoma IoP lowering IoP-independent mechanisms neuroprotection optic nerve optic neuropathy retinal ganglion cells

Suppressive effects of exercise-conditioned serum on cancer cells:A narrative review of the influence of exercise mode,volume,and intensity

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Journal of Sport and Health Science 2024年第4期13卷 484-498,F0003页

作者： Francesco Bettariga Dennis R.Taaffe Daniel A.Galvao Chris Bishop Jin-Soo Kim robert U.Newton Exercise Medicine Research Institute Edith Cowan UniversityJoondalupWA 6027Australia School of Medical and Health Sciences Edith Cowan UniversityJoondalupWA 6027Australia London Sport Institute School of Science and TechnologyMiddlesex UniversityLondonNW44BTUK School of Human Movement and Nutrition Sciences University of QueenslandSt.LuciaQLD 4072Australia

Cancer is a major cause of morbidity and mortality worldwide,and the incidence is increasing,highlighting the need for effective strategies to treat this *** has emerged as fundamental therapeutic medicine in the management of cancer,associated with a lower risk of recur-rence and increased *** avenues of research demonstrate reduction in growth,proliferation,and increased apoptosis of cancer cells,including breast,prostate,colorectal,and lung cancer,when cultured by serum collected after exercise in vitro(i.e.,the cultivation of cancer cell lines in an experimental setting,which simpliﬁes the biological system and provides mechanistic insight into cell responses).The underlying mechanisms of exercise-induced cancer suppressive effects may be attributed to the alteration in circulating factors,such as skeletal muscle-induced cytokines(i.e.,myokines)and ***,exercise-induced tumor suppressive effects and detailed information about training interventions are not well investigated,constraining more precise application of exercise medicine within clinical *** date,it remains unclear what role different training modes(i.e.,resistance and aerobic training)as well as volume and intensity have on exercise-condi-tioned serum and its effects on cancer ***,the available evidence is that a single bout of aerobic training at moderate to vigorous intensity has cancer suppressive effects,while for chronic training interventions,exercise volume appears to be an inﬂuential candidate driving cancer inhibitory effects regardless of training *** for future research investigating training modes,volume and intensity are provided to further our understanding of the effects of exercise-conditioned serum on cancer cells.

关键词： Cancer cells High intensity interval training Moderate intensity continuous training Resistance training Myokines