Extracellular vesicles (EVs) function as potent mediators of intercellular communication for many in vivo processes, contributing to both health and disease related conditions. Given their biological origins and diverse functionality from correspondingly unique “cargo” compositions, both endogenous and modified EVs are garnering attention as promising therapeutic modalities and vehicles for targeted therapeutic delivery applications. Their diversity in composition, however, has revealed a significant need for more comprehensive analytical-based characterization methods, and manufacturing processes that are consistent and scalable. In this review, we explore the dynamic landscape of EV research and development efforts, ranging from novel isolation approaches, to their analytical assessment through novel characterization techniques, and to their production by industrial-scale manufacturing process considerations. Expanding the horizon of these topics to EVs for in-human applications, we underscore the need for stringent development and adherence to Good Manufacturing Practice (GMP) guidelines. Wherein, the intricate interplay of raw materials, production in bioreactors, and isolation practices, along with analytical assessments compliant with the Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines, in conjunction with reference standard materials, collectively pave the way for standardized and consistent GMP production processes.

Carcinoma ; diagnostic imaging ; secondary ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; pathology ; Pancreatic Neoplasms ; diagnostic imaging ; secondary ; Ultrasonography

OBJECTIVETo investigate the effect and molecular mechanism of Tiantai No.1, a compound Chinese herbal preparation, for the prevention and reduction of neurotoxicity induced by beta-amyloid peptides (Abeta) in vitro and its effects on nuclear factor-kappa B (NF-kappa B) and cAMP responsive element-binding protein (CREB) pathways using the gene transfection technique.

METHODSB104 neuronal cells were used to examine the effects of Tiantai No.1 on lowering the neurotoxicity induced by Abeta. The cells were pre-treated with Tiantai No.1 at doses of 50, 100, 150, or 200 micro g/mL respectively for 3 days and co-treated with Tiantai No.1 and beta-amyloid peptide1-40 (A beta 1-40, 10 micro mol/L) for 48 h or post-treated with Tiantai No.1 for 48 h after the cells were exposed to beta-amyloid peptides25-35 (A beta 25-35) for 8 h. In gene transfection assays, cells were treated with Tiantai No.1 at 50 micro g/mL and 150 micro g/mL for 5 days or co-treated with Tiantai No.1 and A beta 1-40 (5 micro mo/L) for 3 days after electroporation for the evaluation of NF-kappa B and CREB expression.

RESULTSPre-treating and co-treating B104 neuronal cells with Tiantai No.1 lowered the neurotoxicity induced by Abeta, and post-treating with Tiantai No.1 reduced or blocked B104 neuronal apoptotic death induced by Abeta (P<0.05, P<0.01). With a dose-dependent relationship, the same treatments increased the expression of NF-kappa B or CREB in B104 neuronal cells (P<0.05, P<0.01). Meanwhile, Tiantai No.1 reduced A beta -40 induced inhibition on NF-kappa B expression (P<0.01).

CONCLUSIONSTiantai No.1 can protect neurons against the neurotoxicity induced by Abeta. The neuroprotective mechanisms may be associated with the activation of NF-kappa B and cAMP cellular signal pathways.

Amyloid beta-Peptides ; Animals ; Apoptosis ; drug effects ; Cells, Cultured ; Cyclic AMP Response Element-Binding Protein ; analysis ; Drugs, Chinese Herbal ; pharmacology ; Electroporation ; Luciferases ; Microscopy, Fluorescence ; NF-kappa B ; analysis ; Neurons ; drug effects ; Rats ; Transfection

Objective: While minimally invasive-transforaminal lumbar interbody fusion (MIS-TLIF) has shown superiority in key clinical metrics over the open approach, evidence regarding patient-reported outcomes remains limited. This study compared postoperative recovery trajectories and symptomatic improvement phases between MIS and open TLIF. Methods: This retrospective review included patients who underwent single-level MIS or open TLIF. Oswestry Disability Index (ODI) and Numerical Rating Scale (NRS) for back and leg pain were collected preoperatively and postoperatively. Segmented regression analysis with mixed-effects modeling, allowing for identification of distinct recovery phases, compared symptomatic trends between approaches. Results: Of 324 patients (268 MIS, 56 open), baseline demographics were similar except for greater preoperative leg pain in the MIS group (NRS: 6.0 vs. 5.0, p = 0.027). A segmented regression model identified 4 ODI recovery phases: postoperative disability phase (PDP, day 0 to 13), early improvement phase (day 13 to 28), late improvement phase (day 28 to 110), and plateau phase (later than day 110). The MIS group exhibited significantly lower disability exacerbation during PDP (β = 0.93 vs. 1.42 points per day, p = 0.008). Additionally, the plateau of NRS back occurred significantly earlier in the MIS group than in the open group (MIS, 26.7 ± 2.6 days vs. open, 51.7 ± 6.6 days, p < 0.001). Conclusion MIS-TLIF resulted in lower postoperative disability during the first 2 weeks compared to the open approach. Furthermore, low back pain achieved an earlier plateau in back pain by about 4 weeks in the MIS approach.

Objective: While minimally invasive-transforaminal lumbar interbody fusion (MIS-TLIF) has shown superiority in key clinical metrics over the open approach, evidence regarding patient-reported outcomes remains limited. This study compared postoperative recovery trajectories and symptomatic improvement phases between MIS and open TLIF. Methods: This retrospective review included patients who underwent single-level MIS or open TLIF. Oswestry Disability Index (ODI) and Numerical Rating Scale (NRS) for back and leg pain were collected preoperatively and postoperatively. Segmented regression analysis with mixed-effects modeling, allowing for identification of distinct recovery phases, compared symptomatic trends between approaches. Results: Of 324 patients (268 MIS, 56 open), baseline demographics were similar except for greater preoperative leg pain in the MIS group (NRS: 6.0 vs. 5.0, p = 0.027). A segmented regression model identified 4 ODI recovery phases: postoperative disability phase (PDP, day 0 to 13), early improvement phase (day 13 to 28), late improvement phase (day 28 to 110), and plateau phase (later than day 110). The MIS group exhibited significantly lower disability exacerbation during PDP (β = 0.93 vs. 1.42 points per day, p = 0.008). Additionally, the plateau of NRS back occurred significantly earlier in the MIS group than in the open group (MIS, 26.7 ± 2.6 days vs. open, 51.7 ± 6.6 days, p < 0.001). Conclusion MIS-TLIF resulted in lower postoperative disability during the first 2 weeks compared to the open approach. Furthermore, low back pain achieved an earlier plateau in back pain by about 4 weeks in the MIS approach.

Objective: While minimally invasive-transforaminal lumbar interbody fusion (MIS-TLIF) has shown superiority in key clinical metrics over the open approach, evidence regarding patient-reported outcomes remains limited. This study compared postoperative recovery trajectories and symptomatic improvement phases between MIS and open TLIF. Methods: This retrospective review included patients who underwent single-level MIS or open TLIF. Oswestry Disability Index (ODI) and Numerical Rating Scale (NRS) for back and leg pain were collected preoperatively and postoperatively. Segmented regression analysis with mixed-effects modeling, allowing for identification of distinct recovery phases, compared symptomatic trends between approaches. Results: Of 324 patients (268 MIS, 56 open), baseline demographics were similar except for greater preoperative leg pain in the MIS group (NRS: 6.0 vs. 5.0, p = 0.027). A segmented regression model identified 4 ODI recovery phases: postoperative disability phase (PDP, day 0 to 13), early improvement phase (day 13 to 28), late improvement phase (day 28 to 110), and plateau phase (later than day 110). The MIS group exhibited significantly lower disability exacerbation during PDP (β = 0.93 vs. 1.42 points per day, p = 0.008). Additionally, the plateau of NRS back occurred significantly earlier in the MIS group than in the open group (MIS, 26.7 ± 2.6 days vs. open, 51.7 ± 6.6 days, p < 0.001). Conclusion MIS-TLIF resulted in lower postoperative disability during the first 2 weeks compared to the open approach. Furthermore, low back pain achieved an earlier plateau in back pain by about 4 weeks in the MIS approach.

Objective: While minimally invasive-transforaminal lumbar interbody fusion (MIS-TLIF) has shown superiority in key clinical metrics over the open approach, evidence regarding patient-reported outcomes remains limited. This study compared postoperative recovery trajectories and symptomatic improvement phases between MIS and open TLIF. Methods: This retrospective review included patients who underwent single-level MIS or open TLIF. Oswestry Disability Index (ODI) and Numerical Rating Scale (NRS) for back and leg pain were collected preoperatively and postoperatively. Segmented regression analysis with mixed-effects modeling, allowing for identification of distinct recovery phases, compared symptomatic trends between approaches. Results: Of 324 patients (268 MIS, 56 open), baseline demographics were similar except for greater preoperative leg pain in the MIS group (NRS: 6.0 vs. 5.0, p = 0.027). A segmented regression model identified 4 ODI recovery phases: postoperative disability phase (PDP, day 0 to 13), early improvement phase (day 13 to 28), late improvement phase (day 28 to 110), and plateau phase (later than day 110). The MIS group exhibited significantly lower disability exacerbation during PDP (β = 0.93 vs. 1.42 points per day, p = 0.008). Additionally, the plateau of NRS back occurred significantly earlier in the MIS group than in the open group (MIS, 26.7 ± 2.6 days vs. open, 51.7 ± 6.6 days, p < 0.001). Conclusion MIS-TLIF resulted in lower postoperative disability during the first 2 weeks compared to the open approach. Furthermore, low back pain achieved an earlier plateau in back pain by about 4 weeks in the MIS approach.

Objective: While minimally invasive-transforaminal lumbar interbody fusion (MIS-TLIF) has shown superiority in key clinical metrics over the open approach, evidence regarding patient-reported outcomes remains limited. This study compared postoperative recovery trajectories and symptomatic improvement phases between MIS and open TLIF. Methods: This retrospective review included patients who underwent single-level MIS or open TLIF. Oswestry Disability Index (ODI) and Numerical Rating Scale (NRS) for back and leg pain were collected preoperatively and postoperatively. Segmented regression analysis with mixed-effects modeling, allowing for identification of distinct recovery phases, compared symptomatic trends between approaches. Results: Of 324 patients (268 MIS, 56 open), baseline demographics were similar except for greater preoperative leg pain in the MIS group (NRS: 6.0 vs. 5.0, p = 0.027). A segmented regression model identified 4 ODI recovery phases: postoperative disability phase (PDP, day 0 to 13), early improvement phase (day 13 to 28), late improvement phase (day 28 to 110), and plateau phase (later than day 110). The MIS group exhibited significantly lower disability exacerbation during PDP (β = 0.93 vs. 1.42 points per day, p = 0.008). Additionally, the plateau of NRS back occurred significantly earlier in the MIS group than in the open group (MIS, 26.7 ± 2.6 days vs. open, 51.7 ± 6.6 days, p < 0.001). Conclusion MIS-TLIF resulted in lower postoperative disability during the first 2 weeks compared to the open approach. Furthermore, low back pain achieved an earlier plateau in back pain by about 4 weeks in the MIS approach.

OBJECTIVETo study the effect of Tiantai No. 1 [symbol in text] on gene expression profile in hippocampus of Alzheimer's disease (AD) rat, molecular genetic target points of the effect of this drug were defined, its molecular genetic pharmacodynamic mechanism of anti-AD was further explored at molecular gene level, and a scientific basis was provided for its clinical availability and promotion.

METHODSThirty male Sprague-Dawley rats were divided into three groups with 10 rats per group: sham-operation group, model group and Tiantai No. 1 group. Sterile surgical procedure was applied, the model group with bilateral hippocampal injection of Aβ1-40 was established, and normal saline was used instead of Aβ1-40 in the sham-operation group. One week after the models was made, rats were administered by gastric lavage once every day for three consecutive weeks. The rats of the sham-operation group and the model group were daily fed with purified water by lavage; the rats of the Tiantai No.1 group treated group were administered with Tiantai No.1 by lavage. Total RNAs of hippocampus tissues were extracted with Trizol, the changes of hippocampus gene expression profiles in the above three groups were analyzed by using Affymetrix rat whole genome expression profile microarray.

RESULTSMicroarray analysis showed that, compared with the sham-operation group, the hippocampus of the model group had 50 up-regulated genes with significant difference (fold change >2), and 21 down-regulated genes with significant difference (fold change <0.5); compared with the hippocampus of the model group, the hippocampus of the Tiantai No. 1 group was found to have 5 up-regulated genes with significant difference (fold change >2) and 20 down-regulated genes with significant difference (fold change <0.5). The functions of differentially expressed genes of the groups were involved in nervous system's development, neuronic differentiation and function-regulation, cellular growth and differentiation and apoptosis, synaptic occurrence and plasticity, inflammation and immune response, ion channels/transporters, cellular signal transduction, cellular material/energy metabolism and so on.

CONCLUSIONTiantai No. 1 can regulate hippocampal function, and further regulate the brain function of animals in multiple gene target points by a number of ways.

Alzheimer Disease ; genetics ; pathology ; Animals ; Body Weight ; drug effects ; Computational Biology ; methods ; Drugs, Chinese Herbal ; pharmacology ; Electrophoresis, Agar Gel ; Gene Expression Profiling ; Gene Expression Regulation ; drug effects ; Hippocampus ; drug effects ; metabolism ; pathology ; Male ; Nucleic Acid Denaturation ; Organ Size ; drug effects ; RNA ; isolation & purification ; metabolism ; Rats, Sprague-Dawley