Clinical Values of Whole-Body Blood Pool Scans and SPECT for Evaluation of Congenital Vascular Malformation.

Purpose: This study examines the diagnostic potential of whole-body blood pool scintigraphy (WBBPS) using technetium-99 m-labeled red blood cells to detect congenital vascular malformations (CVMs). It aims to compare its efficacy with traditional imaging techniques such as magnetic resonance imaging (MRI) and ultrasonography (USG), emphasizing its potential advantages in terms of characterization of lesions and capacity for whole-body assessment. Methods: The efficacy of WBBPS and single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging in diagnosing CVMs, comparing them with USG and MRI results, was evaluated in this retrospective study. Of the 38 patients, 21 were evaluated using these diagnostic methods, with CVMs classified according to the International Society for the Study of Vascular Anomalies guidelines. Also, this study aimed to elucidate the characteristics between WBBPS, SPECT/CT, USG, or MRI findings and their consistency with the final diagnosis. Results: A total of 21 participants were included in this study, with an average age of 17.7 years old, with female predominance (57.1%). The most common diagnosis was vascular malformations (VMs) (71.4%), followed by combined vascular malformations (14.3%) and lymphatic malformations (9.5%). WBBPS demonstrated positive results in 95.2% of cases. Distinct imaging patterns for each condition were observed, with WBBPS being crucial in locating lesions. Conclusion: The study findings suggested that WBBPS with SPECT/CT could be helpful in detecting occult VM lesions and ruling out a lymphatic malformation diagnosis. Thus, it can be employed in the evaluation of CVMs.

Smart Nanoscale Extracellular Vesicles in the Brain: Unveiling their Biology, Diagnostic Potential, and Therapeutic Applications.

Information exchange is essential for the brain, where it communicates the physiological and pathological signals to the periphery and vice versa. Extracellular vesicles (EVs) are a heterogeneous group of membrane-bound cellular informants actively transferring informative calls to and from the brain via lipids, proteins, and nucleic acid cargos. In recent years, EVs have also been widely used to understand brain function, given their "cell-like" properties. On the one hand, the presence of neuron and astrocyte-derived EVs in biological fluids have been exploited as biomarkers to understand the mechanisms and progression of multiple neurological disorders; on the other, EVs have been used in designing targeted therapies due to their potential to cross the blood-brain-barrier (BBB). Despite the expanding literature on EVs in the context of central nervous system (CNS) physiology and related disorders, a comprehensive compilation of the existing knowledge still needs to be made available. In the current review, we provide a detailed insight into the multifaceted role of brain-derived extracellular vesicles (BDEVs) in the intricate regulation of brain physiology. Our focus extends to the significance of these EVs in a spectrum of disorders, including brain tumors, neurodegenerative conditions, neuropsychiatric diseases, autoimmune disorders, and others. Throughout the review, parallels are drawn for using EVs as biomarkers for various disorders, evaluating their utility in early detection and monitoring. Additionally, we discuss the promising prospects of utilizing EVs in targeted therapy while acknowledging the existing limitations and challenges associated with their applications in clinical scenarios. A foundational comprehension of the current state-of-the-art in EV research is essential for informing the design of future studies.

Comparison of Recombinant Human Thyroid-Stimulating Hormone and Thyroid Hormone Withdrawal for 131 I Therapy in Patients With Intermediate- to High-Risk Thyroid Cancer : A Systematic Review and Meta-analysis.

BACKGROUND: This meta-analysis and systematic review aimed to evaluate the therapeutic efficacy and advantages associated with the use of recombinant human thyroid-stimulating hormone (rhTSH) for radioactive iodine (RAI) therapy in patients with intermediate- to high-risk differentiated thyroid cancer. PATIENTS AND METHODS: MEDLINE, EMBASE, and Cochrane databases were searched to identify relevant articles reporting clinical outcomes of rhTSH compared with thyroid hormone withdrawal (THW) in patients with intermediate- to high-risk differentiated thyroid cancer published between January 2012 and June 2023. Meta-analyses were performed (PROSPERO registration number: CRD42022340915) to assess the success rate of radioiodine remnant ablation (RRA) in patients with intermediate to high risk and determine the disease control rate among patients with distant metastases, evaluated using the RECIST criteria. RESULTS: Thirteen studies involving 1858 patients were included in the meta-analysis. Pooled analyses revealed significantly higher overall RRA success rate in the rhTSH group compared with the THW group, with a risk ratio (RR) of 1.12 (95% confidence interval [CI], 1.01-1.25). However, in the subgroup analysis of high-risk patients, pooled analyses showed no significant differences in RRA success rate between the rhTSH group compared with the THW group with a pooled RR of 1.05 (95% CI, 0.88-1.24). In patients with distant metastases, there were no significant differences in the disease control rate between groups, with a pooled RR of 1.06 (95% CI, 0.78-1.44). CONCLUSIONS: rhTSH for RAI therapy is a practical option for RAI therapy in patients with intermediate- to high-risk thyroid cancer, including those with distant metastases.

Clinical Implications of Adding SPECT/CT to Radioiodine Whole-Body Scan in Patients With Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis.

PURPOSE: This study aimed to determine the usefulness of adding SPECT/CT to radioiodine whole-body scans (WBSs) for the treatment of differentiated thyroid cancer (DTC). PATIENTS AND METHODS: A systematic review and meta-analysis were performed following the PRISMA guidelines (PROSPERO registration: CRD42022341732) to compare the feasibility of conclusive readings and the frequency of changes in treatment plans in patients with DTC undergoing WBS + SPECT/CT versus WBS. MEDLINE, EMBASE, and Cochrane databases were searched to identify relevant articles concerning thyroid cancer, radioactive iodine, and SPECT/CT or SPECT, published before August 16, 2023. Studies not comparing WBS + SPECT/CT with WBS, those lacking target outcomes, and those not involving human subjects were excluded. The risk of bias was assessed using the RoBANS 2.0 (Risk of Bias Assessment Tool for Nonrandomized Studies) tool. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system was used to evaluate the quality of evidence and strength of recommendations. RESULTS: A total of 30 studies (prospective n = 9, retrospective n = 21) were included in the meta-analyses. Adding SPECT/CT to WBS was shown to increase conclusive readings for cervical lesions, extracervical lesions, and all regions. Lesion-based analyses showed improvements of 14%, 20%, and 18%, respectively, whereas scan-based analyses showed improvements of 27%, 9%, and 34%. The addition of SPECT/CT to WBS led to changes in 30% of treatment plans after diagnostic scans and 9% of treatment plans after posttherapeutic scans. The quality of evidence and strength of recommendations were low. CONCLUSIONS: Compelling evidence demonstrates that the addition of SPECT/CT to WBS improves lesion localization, diagnostic performance, and therapy plan for patients with DTC.

Predictive factors for severe radiation-induced lung injury in patients with lung cancer and coexisting interstitial lung disease.

BACKGROUND AND PURPOSE: This study aimed to investigate the predictive factors of severe radiation-induced lung injury (RILI) in patients with lung cancer and coexisting interstitial lung disease (ILD) undergoing conventionally fractionated thoracic radiotherapy. MATERIALS AND METHODS: The study includes consecutive patients treated with thoracic radiotherapy for lung cancer at two tertiary centers between 2010 and 2021. RILI severity was graded using the National Cancer Institute Common Terminology Criteria version 5.0, with severe RILI defined as toxicity grade ≥4, and symptomatic RILI as grade ≥2. The absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and C-reactive protein were collected within 4 weeks before starting radiotherapy. Neutrophil-lymphocyte ratios (NLR) were calculated as ANC/ALC. The median follow-up was 9 (range, 6-114) months. RESULTS: Among 54 patients, 22 (40.7 %) had severe RILI. On multivariate logistic regression analysis, high pretreatment ANC (p = 0.030, OR = 4.313), pretreatment NLR (p = 0.007, OR = 5.784), and ILD severity (p = 0.027, OR = 2.416) were significant predictors of severe RILI. Dosimetric factors were not associated with severe RP. Overall survival was significantly worse for patients with severe RILI than those without, with 1-year cumulative overall survival rates of 7.4 % and 62.8 %, respectively. CONCLUSION: Pretreatment blood NLR, ANC, and ILD severity were associated with severe RILI. Overall survival was dismal for patients with severe RILI.

Impact of Positron Emission Tomography Viability Imaging: Guided Revascularizations on Clinical Outcomes in Patients With Myocardial Scar on Single-Photon Emission Computed Tomography Scans.

BACKGROUND: Positron emission tomography (PET) viability scan is used to determine whether patients with a myocardial scar on single-photon emission computed tomography (SPECT) may need revascularization. However, the clinical utility of revascularization decision-making guided by PET viability imaging has not been proven yet. The purpose of this study was to investigate the impact of PET to determine revascularization on clinical outcomes. METHODS: Between September 2012 and May 2021, 53 patients (37 males; mean age = 64 ± 11 years) with a myocardial scar on MIBI SPECT who underwent PET viability test were analyzed in this study. The primary outcome was a temporal change in echocardiographic findings. The secondary outcome was all-cause mortality. RESULTS: Viable myocardium was presented by PET imaging in 29 (54.7%) patients. Revascularization was performed in 26 (49.1%) patients, including 18 (34.0%) with percutaneous coronary intervention (PCI) and 8 (15.1%) with coronary artery bypass grafting. There were significant improvements in echocardiographic findings in the revascularization group and the viable myocardium group. All-cause mortality was significantly lower in the revascularization group than in the medical therapy-alone group (19.2% vs. 44.4%, log-rank P = 0.002) irrespective of viable (21.4% vs. 46.7%, log-rank P = 0.025) or non-viable myocardium (16.7% vs. 41.7%, log-rank P = 0.046). All-cause mortality was significantly lower in the PCI group than in the medical therapy-alone group (11.1% vs. 44.4%, log-rank P < 0.001). CONCLUSION: Revascularization improved left ventricular systolic function and survival of patients with a myocardial scar on SPECT scans, irrespective of myocardial viability on PET scans.

Comparison of Prognostic Value Between Stimulated and Nonstimulated Thyroglobulins in Differentiated Thyroid Cancer: A Retrospective Study.

Purpose: The growing incidence of differentiated thyroid cancer (DTC) demands dependable prognostic factors to guide follow-up and treatment plans. This study investigated the prognostic value of response to therapy (RTT) assessment using TSH stimulated-thyroglobulin (sti-Tg) and nonstimulated-thyroglobulin (nonsti-Tg) and evaluates whether RTT using nonsti-Tg (nonstiRTT) can replace RTT using sti-Tg (stiRTT) in clinical practice to improve patients' quality of life during assessment. Methods: We enrolled 419 DTC patients who underwent total thyroidectomy, radioactive iodine (RAI) therapy, and Tg assessment. Patients with structural incomplete responses were excluded. Initial RTT assessments based on the 2015 American Thyroid Association guidelines (excellent response; ER, indeterminate response, biochemical incomplete response) were performed 6-24 months after RAI therapy. The second RTT assessments were performed 6-24 months after the first assessment. Statistical analysis for recurrence-free survival (RFS) was done with the log-rank test for stiRTT and nonstiRTT. Results: Although initial stiRTT and nonstiRTT were significant predictors for RFS (p < 0.0001), stiRTT provided better RFS prediction than nonstiRTT. The RFS analysis of the second RTT assessment demonstrated statistical significance only for stiRTT (p < 0.0001). In 116 patients classified as ER on initial stiRTT, there was no RFS difference between patients classified as ER on either second stiRTT or nonstiRTT. Conclusion: The prognostic power of stiRTT surpasses that of nonstiRTT in both the initial and second RTT assessment. Nevertheless, among patients classified as ER on initial stiRTT, a second stiRTT may not be required for those classified as ER on the second nonstiRTT. Supplementary Information: The online version contains supplementary material available at 10.1007/s13139-023-00811-8.

Second Primary Malignancy After Radioiodine Therapy in Thyroid Cancer Patient: A Nationwide Study.

Objective: This study aimed to investigate the risk of second primary malignancy after radioiodine (RAI) therapy in patients with thyroid cancer, using the National Health Insurance Service (NHIS) database. Methods: We extracted data from the NHIS database of South Korea, which covers the entire population of the nation. Risk of second primary malignancy in the thyroid cancer patients who received RAI therapy were compared with the thyroid cancer patients who received surgery only. Results: Between January 1, 2004, and December 31, 2018, we identified 363,155 patients who underwent thyroid surgery due to thyroid cancer for analysis. The surgery only cohort was 215,481, and the RAI cohort was 147,674 patients. A total of 19,385 patients developed second primary malignancy (solid cancer, 18,285; hematologic cancer, 1,100). There was no significant increase in the risk of second primary malignancy in patients who received a total cumulative dose of 100 mCi or less (hazard ratio [HR], 1.013; 95% confidence interval [CI], 0.979-1.049). However, a statistically significant increase in the risk of second primary malignancy was observed in patients who received 101-200 mCi (HR, 1.214; 95% CI, 1.167-1.264), 201-300 mCi (HR, 1.422; 95% CI, 1.258-1.607), and > 300 mCi (HR, 1.693; 95% CI, 1.545-1.854). Conclusion: Total cumulative doses of 100 mCi or less of RAI can be safely administered without concerns about second primary malignancy. However, the risk of second primary malignancy increases in a dose-dependent manner, and the risk-benefit needs to be considered for doses over 100 mCi of RAI therapy.

The Diagnostic Value of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Differentiated Thyroid Cancer Patients with Elevated Thyroglobulin/Thyroglobulin Antibody Levels and Negative Iodine Scintigraphy: A Systematic Review and Meta-Analysis.

Background: The objective of this study is to evaluate the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in detecting recurrence in patients with differentiated thyroid cancer (DTC) who have negative whole-body scans (WBSs) but elevated serum thyroglobulin (Tg) or thyroglobulin antibody (TgAb) levels. Methods: This systematic review/meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy criteria (International Prospective Register of Systematic Reviews registration number: CRD42022340924). A comprehensive search of the MEDLINE, EMBASE, and Cochrane databases identified articles reporting the diagnostic accuracy of FDG PET/CT for the detection of recurrence in patients with DTC with negative WBS and elevated serum Tg or TgAb levels published between January 2012 and June 2023. Meta-analyses were performed to determine the diagnostic accuracy of FDG PET/CT on the total target population as well as on subgroups stratified by serum Tg or TgAb, and thyrotropin (TSH) stimulation status at the time of FDG PET/CT. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was applied to evaluate the quality of evidence and the strength of recommendations to facilitate translation of the meta-analysis results into practical recommendations for clinical guidelines. Results: A total of 24 studies involving 1988 patients were included for analysis. The overall pooled sensitivity and specificity values were 0.87 (95% confidence interval [CI] = 0.83-0.92; I2 = 75%) and 0.84 (CI = 0.80-0.89; I2 = 44%), respectively. Subgroup analyses revealed no significant differences in the diagnostic accuracy of FDG PET/CT in patients stratified by serum Tg or TgAb levels, and TSH stimulation status at the time of PET/CT. Treatment plans were changed following FDG PET/CT imaging in 40% (CI = 34-47%; I2 = 39%) of cases. The quality level of evidence for using FDG PET/CT was moderate in both sensitivity and specificity according to the GRADE system. Conclusion: There is moderate quality evidence demonstrating the high diagnostic accuracy of FDG PET/CT in detecting recurrence in patients with DTC with negative WBS and elevated serum Tg or TgAb levels. This evidence corroborates the current guidelines' endorsement of FDG PET/CT as a diagnostic tool in such patients.

An update on stem cell and stem cell-derived extracellular vesicle-based therapy in the management of Alzheimer's disease.

Globally, neurological diseases pose a major burden to healthcare professionals in terms of the management and prevention of the disorder. Among neurological diseases, Alzheimer's disease (AD) accounts for 50%-70% of dementia and is the fifth leading cause of mortality worldwide. AD is a progressive, degenerative neurological disease, with the loss of neurons and synapses in the cerebral cortex and subcortical regions. The management of AD remains a debate among physicians as no standard and specific "disease-modifying" modality is available. The concept of 'Regenerative Medicine' is aimed at regenerating the degenerated neural tissues to reverse the pathology in AD. Genetically modified engineered stem cells modify the course of AD after transplantation into the brain. Extracellular vesicles (EVs) are an emerging new approach in cell communication that involves the transfer of cellular materials from parental cells to recipient cells, resulting in changes at the molecular and signaling levels in the recipient cells. EVs are a type of vesicle that can be transported between cells. Many have proposed that EVs produced from mesenchymal stem cells (MSCs) may have therapeutic promise in the treatment of AD. The biology of AD, as well as the potential applications of stem cells and their derived EVs-based therapy, were explored in this paper.

Three-dimensional culture conditioned bone marrow MSC secretome accelerates wound healing in a burn injury mouse model.

Mesenchymal stem cell (MSC)-based therapy has emerged as a promising regenerative therapeutic approach for wound healing. To determine the effects of cultured MSCs as a 2D monolayer (2D-MSCs) and 3D spheroids (3D-MSCs) on their secretomes, and to examine the effect of 3D-MSC secretomes on endothelial cells (ECs) and MSCs in a burn injury mouse model. MSCs were cultured as 2D monolayers (2D-MSCs) and 3D spheroids (3D-MSCs) and their cellular characteristics were evaluated by western blotting. 2D-MSC and 3D-MSC secretomes (condition medium: CM) were analyzed using an angiogenic array. The activation of ECs by 2D-MSC and 3D-MSC CMs was examined in cellular proliferation, migration, and tube formation assays. The wound healing effects of 2D-MSCs and 3D-MSCs were determined in vivo using a burn injury mouse model. 3D culture conditions altered the markers of components that regulate cell survival, cytoskeletal, adhesion, and proliferation. Interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA), IL-8, and chemokine (CXC motif) ligand 1 (CXCL1) were present at high levels in the CM of 3D-MSCs compared with 2D-MCs. 3D-MSC-CMs promoted the proliferation, migration, and tube formation of ECs. Furthermore, 3D-MSC treatment enhanced wound healing in a burn injury mouse model. 3D culture improves proangiogenic factors in the MSC secretome and 3D-MSCs represent a new cell-based treatment strategy for wound healing.

Engineered Nanovesicles from Fibroblasts Modulate Dermal Papillae Cells In Vitro and Promote Human Hair Follicle Growth Ex Vivo.

Alopecia is a common medical condition affecting both sexes. Dermal papilla (DP) cells are the primary source of hair regeneration in alopecia patients. Therapeutic applications of extracellular vesicles (EVs) are restricted by low yields, high costs, and their time-consuming collection process. Thus, engineered nanovesicles (eNVs) have emerged as suitable therapeutic biomaterials in translational medicine. We isolated eNVs by the serial extrusion of fibroblasts (FBs) using polycarbonate membrane filters and serial and ultracentrifugation. We studied the internalization, proliferation, and migration of human DP cells in the presence and absence of FB-eNVs. The therapeutic potential of FB-eNVs was studied on ex vivo organ cultures of human hair follicles (HFs) from three human participants. FB-eNVs (2.5, 5, 7.5, and 10 µg/mL) significantly enhanced DP cell proliferation, with the maximum effect observed at 7.5 µg/mL. FB-eNVs (5 and 10 µg/mL) significantly enhanced the migration of DP cells at 36 h. Western blotting results suggested that FB-eNVs contain vascular endothelial growth factor (VEGF)-a. FB-eNV treatment increased the levels of PCNA, pAKT, pERK, and VEGF-receptor-2 (VEGFR2) in DP cells. Moreover, FB-eNVs increased the human HF shaft size in a short duration ex vivo. Altogether, FB-eNVs are promising therapeutic candidates for alopecia.

Different Expression of Thyroid-Specific Proteins in Thyroid Cancer Cells between 2-Dimensional (2D) and 3-Dimensional (3D) Culture Environment.

The two-dimensional (2D) monolayer culture as a conventional method has been widely applied in molecular biology fields, but it has limited capability to recapitulate real cell environments, being prone to misinterpretation with poor prediction of in vivo behavior. Recently, the three-dimensional (3D) spheroid culture has been studied extensively. Spheroids are self-assembled cell aggregates that have biomimicry capabilities. The behavior of thyroid cancer under the 3D spheroid culture environment has been studied; however, there are no reports regarding differences in the degree of thyroid cancer cell differentiation under 2D and 3D culture conditions. This study investigated the expression of thyroid differentiation proteins related to iodide-metabolizing mechanisms in thyroid cancer cells under different culture conditions. Four thyroid cancer cell lines and one thyroid follicular epithelial cell line were grown in adherent 2D cell culture and 3D spheroid culture with agarose-coated plates. We observed changes in proliferation, hypoxia, extracellular matrix (ECM), cytoskeleton, thyroid-specific proteins, and thyroid transcription factors. All cell lines were successfully established in the spheroid following cell aggregation. Proliferation considerably decreased, while hypoxia-inducible factor 1-α(HIF1-α) was promoted in 3D spheroids; moreover, 3D spheroids with thyroid cancers showed diminished thyroid differentiation markers, but thyroid follicular epithelial cells revealed either a maintenance or weak decline of protein expression. We verified that the 3D spheroid culture environment can be similar to in vivo conditions because of its alterations in numerous cellular and functional activities, including morphology, cellular proliferation, viability, hypoxia, ECM, cytoskeleton, and thyroid differentiation, compared to the conventional 2D monolayer culture environment. An in vitro experimental study using 3D spheroid culture is ideal for the faster discovery of new drugs.

Application of extracellular vesicles from mesenchymal stem cells promotes hair growth by regulating human dermal cells and follicles.

BACKGROUND: Dermal papillae (DP) and outer root sheath (ORS) cells play important roles in hair growth and regeneration by regulating the activity of hair follicle (HF) cells. AIM: To investigate the effects of human mesenchymal stem cell-derived extracellular vesicles (hMSC-EVs) on DP and ORS cells as well as HFs. EVs are known to regulate various cellular functions. However, the effects of hMSC-EVs on hair growth, particularly on human-derived HF cells (DP and ORS cells), and the possible mechanisms underlying these effects are unknown. METHODS: hMSC-EVs were isolated and characterized using transmission electron micro scopy, nanoparticle tracking analysis, western blotting, and flow cytometry. The activation of DP and ORS cells was analyzed using cellular proliferation, migration, western blotting, and real-time polymerase chain reaction. HF growth was evaluated ex vivo using human HFs. RESULTS: Wnt3a is present in a class of hMSC-EVs and associated with the EV membrane. hMSC-EVs promote the proliferation of DP and ORS cells. Moreover, they translocate ß-catenin into the nucleus of DP cells by increasing the expression of ß-catenin target transcription factors (Axin2, EP2 and LEF1) in DP cells. Treatment with hMSC-EVs also promoted the migration of ORS cells and enhanced the expression of keratin (K) differentiation markers (K6, K16, K17, and K75) in ORS cells. Furthermore, treatment with hMSC-EVs increases hair shaft elongation in cultured human HFs. CONCLUSION: These findings suggest that hMSC-EVs are potential candidates for further preclinical and clinical studies on hair loss treatment.

Interleukin-4 Receptor Targeting Peptide Decorated Extracellular Vesicles as a Platform for In Vivo Drug Delivery to Thyroid Cancer.

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been demonstrated to deliver therapeutic drugs in preclinical studies. However, their use is limited, as they lack the ability to specifically deliver drugs to tumor tissues in vivo. In the present study, we propose the use of a targeting peptide, IL-4R-binding peptide (IL4RPep-1), to specifically deliver intravenously (i.v.) infused EVs to thyroid tumors. In vivo, a xenograft tumor model was treated with either the control peptide (NSSSVDK) or IL4RPep-1-Flamma; mice were fluorescently imaged (FLI) using an in vivo imaging system at 0-3 h post-treatment. EVs (labeled with DiD dye) were conjugated with IL4RPep-1 through a DOPE-NHS linker and administered to mice intravenously. FLI was performed 0-24 h post-injection, and the animals were sacrificed for further experiments. The morphology and size of EVs, the presence of EV markers such as CD63 and ALIX, and the absence of the markers GM130 and Cyto-C were confirmed. In vivo, FLI indicated an accumulation of i.v. injected IL4RPep-1-Flamma at the tumor site 90 min post-injection. No accumulation of NSSSVDK-Flamma was detected. In vivo, IL4RPep-1-EVs targeted the Cal-62 tumor 2 h post-injection. NSSSVDK-EVs were not even detected in the tumor 24 h post-injection. The quantification of FLI showed a significant accumulation of MSC-EVs in the tumor 2 h, 3 h, and 24 h post-injection. Furthermore, ex vivo imaging and an IF analysis confirmed the in vivo findings. Our results demonstrate the use of the IL4RPep-1 peptide as a targeting moiety of EVs for IL-4R-expressing anaplastic thyroid tumors.

Application of Cell-Derived Extracellular Vesicles and Engineered Nanovesicles for Hair Growth: From Mechanisms to Therapeutics.

Hair loss is one of the most common disorders that affect both male and female patients. Cell-derived nanovesicles (CDVs) are natural extracellular vesicles and engineered nanovesicles that can carry various biologicals materials such as proteins, lipids, mRNA, miRNA, and DNA. These vesicles can communicate with local or distant cells and are capable of delivering endogenous materials and exogenous drugs for regenerative therapies. Recent studies revealed that CDVs can serve as new treatment strategies for hair growth. Herein, we review current knowledge on the role of CDVs in applications to hair growth. The in-depth understanding of the mechanisms by which CDVs enable therapeutic effects for hair growth may accelerate successful clinical translation of these vesicles for treating hair loss.

COVID-19 and diabetes: What do we know so far?

Coronavirus disease 2019 (COVID-19) management has been challenging for patients with comorbidities. Patients with diabetes and COVID-19, in particular, have shown severe symptoms and rapid progression of the disease. They also have a high mortality rate compared to the non-diabetic population. The high mortality rate is caused in people with diabetes who are in a pro-inflammatory condition; this could worsen COVID-19. In addition, people with diabetes have circulatory issues and COVID-19 infection can lead to further clotting problems. It is critical to understand the mechanisms underlying the adverse clinical outcomes in patients with diabetes and COVID-19. This review discusses various disease conditions contributing to poor prognosis in diabetic COVID-19 patients such as hyperglycemia, insulin resistance, impaired pancreatic function, and production of advanced glycation end products.

Current understanding of MSC-derived exosomes in the management of knee osteoarthritis.

Mesenchymal stem cell-derived exosomes (MSC-Exos) have been utilized as medicinal agents or as delivery vehicles in cartilage injuries and cartilage-based diseases. Given the ongoing emergence of evidence on the effector mechanisms and methods of the utility of the MSC-Exos in knee osteoarthritis, a comprehensive review of the current evidence is the need of the hour. Hence, in this article, we review the current understanding of the role of MSC-Exos in the management of knee osteoarthritis in view of their classification, characterization, biogenesis, mechanism of action, pathways involved in their therapeutic action, in-vitro evidence on cartilage regeneration, in-vivo evidence in OA knee models and recent advances in using MSC-Exos to better streamline future research from bench to bedside for OA knee.