Enhancing Diabetic Wound Healing Through Improved Angiogenesis: The Role of Emulsion-Based Core-Shell Micro/Nanofibrous Scaffold with Sustained CuO Nanoparticle Delivery.

Attempts are made to design a system for sustaining the delivery of copper ions into diabetic wounds and induce angiogenesis with minimal dose-dependent cytotoxicity. Here, a dual drug-delivery micro/nanofibrous core-shell system is engineered using polycaprolactone/sodium sulfated alginate-polyvinyl alcohol (PCL/SSA-PVA), as core/shell parts, by emulsion electrospinning technique to optimize sustained delivery of copper oxide nanoparticles (CuO NP). Herein, different concentrations of CuO NP (0.2, 0.4, 0.8, and 1.6%w/w) are loaded into the core part of the core-shell system. The morphological, biomechanical, and biocompatibility properties of the scaffolds are fully determined in vitro and in vivo. The 0.8%w/w CuO NP scaffold reveals the highest level of tube formation in HUVEC cells and also upregulates the pro-angiogenesis genes (VEGFA and bFGF) expression with no cytotoxicity effects. The presence of SSA and its interaction with CuO NP, and also core-shell structure sustain the release of the nanoparticles and provide a non-toxic microenvironment for cell adhesion and tube formation, with no sign of adverse immune response in vivo. The optimized scaffold significantly accelerates diabetic wound healing in a rat model. This study strongly suggests the 0.8%w/w CuO NP-loaded PCL/SSA-PVA as an excellent diabetic wound dressing with significantly improved angiogenesis and wound healing.

Fabrication and characterization of a hydrocolloid wound dressing functionalized with human placental derived extracellular matrix for management of skin wounds: An animal study.

BACKGROUND: Functionalization of wound dressing is one of the main approaches for promoting wound healing in skin wound management. In this study, our aim is to fabricate a bio-functionalized hydrocolloid wound dressing. METHODS: The extracellular matrix (ECM) was extracted from human placental tissue. A hydrocolloid film was fabricated using Na-CMC, pectin, gelatin, styrene-isoprene-styrene adhesive, glycerol, and 0.5%-2.5% powdered ECM. A polyurethane film and a release liner were used in the hydrocolloid/ECM films. The mechanical, adhesion, swelling rate, and integrity of the films were investigated. Cell proliferation, adhesion, and migration assays, as well as, SEM and FTIR spectroscopy were also conducted. Macroscopic and microscopic evaluations of wound healing process and formation of blood vessels were conducted in mouse animal models. RESULTS: We successfully fabricated a three-layered ECM-functionalized hydrocolloid dressing with a water vapor transmission rate of 371 g/m2 /day and an adhesion peel strength of 176 KPa. Cellular adhesion, proliferation and migration were promoted by ECM. In the animal tests, ECM-functionalized hydrocolloids significantly improved wound closure and re-epithelialization at days 14 and 21. Also, ECM-functionalized hydrocolloids promoted the formation of hair follicles. CONCLUSIONS: Our findings suggest that ECM could enhance the wound healing properties of hydrocolloid wound dressings. This wound dressing could be considered for application in hard-to-heal acute wounds.

3D-printed PLA/Gel hybrid in liver tissue engineering: Effects of architecture on biological functions.

The liver is one of the vital organs in the body, and the gold standard of treatment for liver function impairment is liver transplantation, which poses many challenges. The specific three-dimensional (3D) structure of liver, which significantly impacts the growth and function of its cells, has made biofabrication with the 3D printing of scaffolds suitable for this approach. In this study, to investigate the effect of scaffold geometry on the performance of HepG2 cells, poly-lactic acid (PLA) polymer was used as the input of the fused deposition modeling (FDM) 3D-printing machine. Samples with simple square and bioinspired hexagonal cross-sectional designs were printed. One percent and 2% of gelatin coating were applied to the 3D printed PLA to improve the wettability and surface properties of the scaffold. Scanning electron microscopy pictures were used to analyze the structural properties of PLA-Gel hybrid scaffolds, energy dispersive spectroscopy to investigate the presence of gelatin, water contact angle measurement for wettability, and weight loss for degradation. In vitro tests were performed by culturing HepG2 cells on the scaffold to evaluate the cell adhesion, viability, cytotoxicity, and specific liver functions. Then, high-precision scaffolds were printed and the presence of gelatin was detected. Also, the effect of geometry on cell function was confirmed in viability, adhesion, and functional tests. The albumin and urea production of the Hexagonal PLA scaffold was about 1.22 ± 0.02-fold higher than the square design in 3 days. This study will hopefully advance our understanding of liver tissue engineering toward a promising perspective for liver regeneration.

Combination of Curcumin and Metformin Inhibits Cell Growth and Induces Apoptosis without Affecting the Cell Cycle in LNCaP Prostate Cancer Cell Line.

Side effects and chemotherapy resistance, demand new therapeutics with minimal side effects. Here, we investigated the combined effect of curcumin and metformin on the LNCaP prostate cancer cell line. LNCaP cells were treated with curcumin, metformin, and their combination at different concentrations. Cell viability was assessed by MTT assay and expression of Bax, Bcl-2, mTOR, hTERT, PUMA, p53 and p21 genes was analyzed by real-time PCR. Apoptosis and cell cycle were assessed by flow cytometry. Our results revealed that the viability of cells treated with curcumin, metformin, and their combination was significantly (P < 0.05) reduced with increasing the concentration and prolonging the treatment time. Meanwhile, the combination showed a synergistic effect within 48 h. In the curcumin treated group, the expression of Bcl-2 and hTERT genes diminished. In the metformin treated group, the expression of Bax and PUMA genes was enhanced while the expression of Bcl-2, hTERT, mTOR, and p53 genes declined. Although all treatments induced apoptosis, the combination of curcumin and metformin showed the maximum level of apoptosis, cytotoxicity, and expression of Bax gene. The combination of curcumin and metformin showed synergistic effects within 48 h. This combination could be a potential therapeutic candidate for prostate cancer to be further investigated.

The secretome of mesenchymal stem cells and oxidative stress: challenges and opportunities in cell-free regenerative medicine.

Over the last decade, mesenchymal stem cells (MSCs) have been considered a suitable source for cell-based therapy, especially in regenerative medicine. First, the efficacy and functions of MSCs in clinical applications have been attributed to their differentiation ability, called homing and differentiation. However, it has recently been confirmed that MSCs mostly exert their therapeutic effects through soluble paracrine bioactive factors and extracellular vesicles, especially secretome. These secreted components play critical roles in modulating immune responses, improving the survival, and increasing the regeneration of damaged tissues. The secretome content of MSCs is variable under different conditions. Oxidative stress (OS) is one of these conditions that is highly important in MSC therapy and regenerative medicine. High levels of reactive oxygen species (ROS) are produced during isolation, cell culture, and transplantation lead to OS, which induces cell death and apoptosis and limits the efficacy of their regeneration capability. In turn, the preconditioning of MSCs in OS conditions contributes to the secretion of several proteins, cytokines, growth factors, and exosomes, which can improve the antioxidant potential of MSCs against OS. This potential of MSC secretome has turned it into a new promising cell-free tissue regeneration strategy.This review provides a view of MSC secretome under OS conditions, focusing on different secretome contents of MSCs and thier possible therapeutic potential against cell therapy.

Improvement, scaling-up, and downstream analysis of exosome production.

Exosomes are the most researched extracellular vesicles. In many biological, physiological, and pathological studies, they have been identified as suitable candidates for treatment and diagnosis of diseases by acting as the carriers of both drugs and genes. Considerable success has been achieved regarding the use of exosomes for tissue regeneration, cancer diagnosis, and targeted drug/gene delivery to specific tissues. While major progress has been made in exosome extraction and purification, extraction of large quantities of exosomes is still a major challenge. This issue limits the scope of both exosome-based research and therapeutic development. In this review, we have aimed to summarize experimental studies focused at increasing the number of exosomes. Biotechnological studies aimed at identifying the pathways of exosome biogenesis to manipulate some genes in order to increase the production of exosomes. Generally, two major strategies are employed to increase the production of exosomes. First, oogenesis pathways are genetically manipulated to overexpress activator genes of exosome biogenesis and downregulate the genes involved in exosome recycling pathways. Second, manipulation of the cell culture medium, treatment with specific drugs, and limiting certain conditions can force the cell to produce more exosomes. In this study, we have reviewed and categorized these strategies. It is hoped that the information presented in this review will provide a better understanding for expanding biotechnological approaches in exosome-based therapeutic development.

Can Postural Instability in Individuals with Distal Radius Fractures Be Alleviated by Concurrent Cognitive Tasks?

BACKGROUND: Although impaired postural control may be a risk factor for distal radius fractures (wrist fractures), which often are caused by falls, little attention has been given thus far to the various performance and neurophysiologic aspects involved. Although studies suggest that external focus and cognitive tasks can improve postural control, it remains unclear whether these benefits are observed in individuals with a history of distal radius fracture and to what extent. QUESTIONS/PURPOSES: (1) To compare patients with a history of distal radius fracture to age- and sex-matched controls in terms of postural stability while standing on stable and unstable support surfaces, using both postural sway and neurophysiological measures as endpoints; and (2) to determine whether internal- and external-focus strategies and cognitive tasks can improve postural stability in these patients. METHODS: Forty patients with distal radius fracture (33 females and seven males with a mean ± SD age of 56 ± 4 years) and 40 sex- and age-matched control participants participated in the study. We recruited patients with a history of fall-induced distal radius fractures occurring between 6 and 24 months before the start of our study. We excluded patients who had any of the following: fear of falling, taking any medication that may affect balance, neurologic disorders, dizziness, vestibular problems, Type II diabetes, musculoskeletal disorders or recent history of lower extremity fracture, any recent surgical interventions in the spine or lower limbs, and/or cognitive impairment. Of 120 patients who were being treated for distal radius fracture over the 18-month period, 91 (76%) agreed to participate and 40 eligible patients were finally enrolled. The control group included sex- and age-matched (within 2-year intervals) individuals who had never had a wrist fracture. This group was selected from attendants/relatives of the patients attending the neurology and physical medicine and rehabilitation outpatient departments, as well as other volunteers with no history of balance problems or wrist fractures. To address our primary research question, we compared the postural control of individuals with a history of distal radius fracture with the control group while quietly standing on different support surfaces (rigid and foam surfaces) using both postural sway measures obtained by a force plate as well as neurophysiological measures (electromyography [EMG] activity of tibialis anterior and medial gastrocnemius). To address our secondary research question, we compared the postural sway measures and EMG activity of the ankle muscles between different experimental conditions (baseline, internal focus (mentally focusing on their feet without looking), external focus (mentally focusing on rectangular papers, placed on the force plate or foam, one under each foot), difficult cognitive task (recalling maximum backward digits plus one) and easy cognitive task (recalling half of the maximum backward digits). RESULTS: Patients with distal radius fractures presented with greater postural sway (postural instability) and enhanced ankle muscle activity compared with their control counterparts, but only while standing on a foam surface (mean velocity: 5.4 ± 0.8 versus 4.80 ± 0.5 [mean difference = 0.59, 95% CI of difference, 0.44-0.73; p < 0.001]; EMG root mean square of the tibialis anterior: 52.2 ± 9.4 versus 39.30 ± 6 [mean difference = 12.9, 95% CI of difference, 11.4-14.5; p < 0.001]). Furthermore, a decrease in postural sway was observed while standing on both rigid and foam surfaces during the external focus, easy cognitive, and difficult cognitive conditions compared with the baseline (for example, mean velocity in the baseline condition compared with external focus, easy cognitive task and difficult cognitive task was: 4.9 ± 1.1 vs 4.7 ± 1 [mean difference = 0.14, 95% CI of difference, 0.11-0.17; p < 0.001], 4.6 ± 1 [mean difference = 0.25, 95% CI of difference, 0.21-0.29; p < 0.001], and 4.5 ± 1 [mean difference = 0.34, 95% CI of difference, 0.29-0.40; p < 0.001] in the wrist fracture group). The same result was obtained for muscle activity while standing on foam (EMG root mean square of tibialis anterior in the baseline condition compared with external focus, easy cognitive task and difficult cognitive task: 58.8 ± 7.2 versus 52.3 ± 6.6 [mean difference = 6.5, 95% CI of difference, 5.5-7.6; p < 0.001], 48.8 ± 7.1 [mean difference = 10.1, 95% CI of difference, 9-11.1; p < 0.001], 42.2 ± 5.3 [mean difference = 16.7 95% CI of difference, 15.1-18.2; p < 0.001] in the wrist fracture group). CONCLUSIONS: The current results suggest that patients with a history of distal radius fractures have postural instability while standing on unstable support surfaces. This instability, which is associated with enhanced ankle muscle activity, conceivably signifying an inefficient cautious mode of postural control, is alleviated by external attention demands and concurrent cognitive tasks. CLINICAL RELEVANCE: The findings of this study may serve as a basis for designing informed patient-specific balance rehabilitation programs and strategies to improve stability and minimize falls in patients with distal radius fractures. The integrative methodology presented in this work can be extended to postural control and balance assessment for various orthopaedic/neurological conditions.

Evaluation of the clinical and radiological outcome of hemi-hamate arthroplasty in the reconstruction of proximal interphalangeal Joint fracture-dislocations.

Background: Hemi-hamate arthroplasty, a new attractive method for treatment of unstable Proximal Interphalangeal (PIP) joint fracture-dislocations, offers several advantages over the previous methods. This study was designed to evaluate the clinical and radiological outcome of this procedure. Methods: In this study, 14 patients and 15 fingers with PIP joint fracture-dislocations were evaluated, including 8 acute and 7 chronic injuries. The mean age and follow-up of the patients were 35.3 years and 29.7 months, respectively. The mean PIP joint involvement was 56.6%. Objective assessment of the outcome was performed by joint alignment, motion, stability, and grip and pinch strength. Subjective evaluation of the outcome was performed using the Visual Analogue Scale (VAS) and Disabilities of the Arm, Shoulder, and Hand (DASH) score. Statistical analysis was performed using SPSS for Windows (version 16). Independent sample t test or Mann-Whitney U test were used for statistical comparison of the mean values. A p value of < 0.05 was considered significant. Results: At the final follow-up, 14 out of 15 PIP joints were clinically stable. Grip and pinch strength of the injured hand averaged 87.6% and 88% of contralateral hand, respectively. The mean PIP joint flexion, arch of motion, and flexion contracture were 82.6, 63.6, and 19 degrees, respectively. The mean DASH score was 20.33±21.87 in acute and 7.25±11.71 in the chronic group (p=0.181). The mean VAS was 2.87±2.29 in acute versus 0.42±0.78 in chronic patients (p=0.022). The degenerative joint disease was observed in 5 cases. Conclusion: Although hemi-hamate arthroplasty is a promising method for the reconstruction of severe PIP joint fracturedislocations, it is associated with minimal functional limitation and high rate of osteoarthritis.

Evaluation of functional outcome after nonsurgical management of terrible triad injuries of the elbow.

BACKGROUND: Terrible triad (TT) is one of the severe injuries of the elbow that generally requires surgery. Nonsurgical treatment has recently been applied in selected cases of TT injury. Evaluation of the results of this treatment was the main aim of this study. METHODS: In a prospective cohort study, 10 patients with a mean follow-up of 30.6 months were evaluated. The inclusion criteria included a congruent joint after closed reduction, no indication for surgery of the coronoid and radial head fractures, no block in supination and pronation up to 60°, no intra-articular fragments, and a free and stable joint with ulnohumeral extension up to a minimum of 45°. Mayo Elbow Performance Index and Disabilities of the Arm, Shoulder, and Hand score were used for assessment of the functional outcome. A standard physical examination to record elbow range of motion was also performed. RESULTS: For the affected and the contralateral elbows, respectively, the mean extension of the elbow was 11° ± 7° and 0.0° ± 2°; the mean flexion was 131° ± 9° and 140° ± 10°; the mean supination was 58° ± 17° and 85 ± 7°; and the mean pronation was 53° ± 23° and 85° ± 7°. The mean Disabilities of the Arm, Shoulder, and Hand score was 4.76 ± 5.17. The mean Mayo Elbow Performance Index was 95 ± 8.16. CONCLUSION: Nonsurgical management of the TT injury can result in acceptable functional outcomes when a patient meets the criteria set for nonsurgical treatment.

Habitual dislocation of the hip: a rare case report.

Habitual dislocation of the hip (HDH) in children is a rare entity and can be a causative factor for popping or snapping hip which is a common problem in children with good prognosis. We report a case of HDH in a 9 year old girl who was suffering from frequent snapping hip at night, its course and treatment process.

Combined Treatment of Dendrosomal-Curcumin and Daunorubicin Synergistically Inhibit Cell Proliferation, Migration and Induce Apoptosis in A549 Lung Cancer Cells.

Purpose: Chemotherapy drugs used to treat lung cancer are associated with drug resistance and severe side effects. There have been rising demands for new therapeutic candidates and novel approaches, including combination therapy. Here, we aimed to investigate the combinatorial effect of a dendrosomal formulation of curcumin (DNC) and daunorubicin (DNR) on the A549 lung cancer cell line. Methods: We performed cytotoxicity, apoptosis, cell migration, colony-formation capacity, and gene expression analysis to interpret the mechanism of action for a combination of DNC and DNR on A549 cells. Results: Our results revealed that the combination of DNC and DNR could synergistically inhibit the A549 cells' growth. This synergistic cytotoxicity was further approved by flow cytometry, migration assessment, colony-forming capacity and gene expression analysis. DNR combination with DNC resulted in increased apoptosis to necrosis ratio compared to DNR alone. In addition, the migration and colony-forming capacity were at the minimal range when DNC was combined with DNR. Combined treatment decreased the expression level of MDR-1, hTERT and Bcl-2 genes significantly. In addition, the ratio of Bax/Bcl2 gene expression significantly increased. Our analysis by free curcumin, dendrosomes and DNC also showed that dendrosomes do not have any significant cytotoxic effect on the A549 cells, suggesting that this carrier has a high potential for enhancing the curcumin's biological effects. Conclusion: Our observations suggest that the DNC formulation of curcumin synergistically enhances the antineoplastic effect of DNR on the A549 cell line through the modulation of apoptosis/necrosis ratio, as well as Bax/Bcl2 ratio, MDR-1 and hTERT gene expression.

Diagnostic accuracy of serum derived exosomes for hepatocellular carcinoma: a systematic review and meta-analysis.

INTRODUCTION: Early and non-invasive detection of hepatocellular carcinoma (HCC), which is usually asymptomatic, can improve overall survival outcomes. The objective of this systematic review and meta-analysis was to evaluate the diagnostic accuracy of serum-derived exosomes for diagnosing HCC. METHODS: PubMed, Web of Science, and Scopus databases were searched for relevant studies up to April 2023. The quality of included studies was assessed using the QUADAS-2 checklist, and data were extracted. Statistical analysis was performed on 18 studies from 3,993 records, and a diagnostic meta-analysis was conducted. Biomarkers were categorized into four groups based on their type (exosomal miRNAs, exosomal RNAs, alpha-fetoprotein (AFP), and exosomal RNAs+AFP panel), and a meta-analysis was conducted for each category separately. RESULTS: The highest pooled sensitivity was 0.86 for exosomal miRNAs, and exosomal RNAs+AFP had the highest pooled specificity; (0.89). Furthermore, exosomal RNAs+AFP had the highest pooled positive likelihood ratio; (7.55), the highest pooled diagnostic odds ratio (35.96) and the highest pooled area under the curve (0.93). Exosomal miRNAs had the lowest pooled negative likelihood ratio; (0.17). CONCLUSIONS: The diagnostic accuracy of exosomal biomarkers is superior to that of AFP, and combining the two in a panel yields the better results.

3D-printed placental-derived bioinks for skin tissue regeneration with improved angiogenesis and wound healing properties.

Extracellular matrix (ECM)-based bioinks has attracted much attention in recent years for 3D printing of native-like tissue constructs. Due to organ unavailability, human placental ECM can be an alternative source for the construction of 3D print composite scaffolds for the treatment of deep wounds. In this study, we use different concentrations (1.5%, 3% and 5%w/v) of ECM derived from the placenta, sodium-alginate and gelatin to prepare a printable bioink biomimicking natural skin. The printed hydrogels' morphology, physical structure, mechanical behavior, biocompatibility, and angiogenic property are investigated. The optimized ECM (5%w/v) 3D printed scaffold is applied on full-thickness wounds created in a mouse model. Due to their unique native-like structure, the ECM-based scaffolds provide a non-cytotoxic microenvironment for cell adhesion, infiltration, angiogenesis, and proliferation. In contrast, they do not show any sign of immune response to the host. Notably, the biodegradation, swelling rate, mechanical property, cell adhesion and angiogenesis properties increase with the increase of ECM concentrations in the construct. The ECM 3D printed scaffold implanted into deep wounds increases granulation tissue formation, angiogenesis, and re-epithelialization due to the presence of ECM components in the construct, when compared with printed scaffold with no ECM and no treatment wound. Overall, our findings demonstrate that the 5% ECM 3D scaffold supports the best deep wound regeneration in vivo, produces a skin replacement with a cellular structure comparable to native skin.

Bilateral combined Monteggia and Galeazzi fractures: a case report.

We present an exceedingly rare case of left Monteggia-Galeazzi fracture-dislocation and right Monteggia-distal radius fracture occurring simultaneously in a 20-year old male patient who had fallen 13 meters from a building. The combination of Monteggia and Galeazzi fracture-dislocation in the same forearm is very rare and, to the best of our knowledge, simultaneous bilateral Monteggia and Galeazzi or distal radius fracture in the same patient, have never been reported.

Protective effect of selenium on vincristine-induced peripheral neuropathy in PC12 cell line.

Vincristine-induced peripheral neuropathy (VIPN) is the main side effect and major reason for neuropathic pain in cancer survivors treated with vincristine. Vincristine, a chemotherapeutic antimitotic drug, is used frequently in combination chemotherapy. The primary purpose of the current study was to assess the protective effect of sodium selenite (SSe) on VIPN in vitro. Cytotoxicity effects of vincristine were evaluated using PC12 cells as a neuronal model. The cell culture studies were conducted in three groups based on the various treatments, including vincristine, SSe, and co-exposure to both compositions. Cell viability and cell cycle analyses were performed using MTT assay and flow cytometry, respectively. The level of mRNA expression of Bax and Bcl-2 was determined using qRT-PCR. According to the results, vincristine decreased the survival rate of PC12 cells. After 24 and 48 h exposure to different concentrations of vincristine (0.1-20 µΜ), the survival rate of PC12 cells decreased as compared to the control group. The results showed that treatment with 5 µΜ of vincristine resulted in apoptosis of PC12 cells. Interestingly,co-incubation of these cells with SSe significantly reduced the cell damage induced by vincristine. Furthermore, vincristine induced the inhibition of the G2 phase in PC 12 cells, and using SSe in combination with vincristine eliminated the inhibition of the cell cycle in the G2 phase. Briefly, our in vitro preliminary study showed that SSe might protect PC12 cells from vincristine-induced peripheral neuropathy during chemotherapy.

Liquid Biopsy-Based Biosensors for MRD Detection and Treatment Monitoring in Non-Small Cell Lung Cancer (NSCLC).

Globally, non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths. Despite advancements in chemotherapy and targeted therapies, the 5-year survival rate has remained at 16% for the past forty years. Minimal residual disease (MRD) is described as the existence of either isolated tumour cells or circulating tumour cells in biological liquid of patients after removal of the primary tumour without any clinical signs of cancer. Recently, liquid biopsy has been promising as a non-invasive method of disease monitoring and treatment guidelines as an MRD marker. Liquid biopsy could be used to detect and assess earlier stages of NSCLC, post-treatment MRD, resistance to targeted therapies, immune checkpoint inhibitors (ICIs) and tumour mutational burden. MRD surveillance has been proposed as a potential marker for lung cancer relapse. Principally, biosensors provide the quantitative analysis of various materials by converting biological functions into quantifiable signals. Biosensors are usually operated to detect antibodies, enzymes, DNA, RNA, extracellular vesicles (EVs) and whole cells. Here, we present a category of biosensors based on the signal transduction method for identifying biosensor-based biomarkers in liquid biopsy specimens to monitor lung cancer treatment.

A review of potential suggested drugs for coronavirus disease (COVID-19) treatment.

The latest pandemic, coronavirus disease-2019 (COVID-19), is associated with high prevalence and easy transmission, which is expanding globally with no conventional treatment or vaccine. The new virus revealed 79% and 50% genomic similarities with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively. Accordingly, since the disease resists testing and adopting new therapeutics, repositioning pre-existing drugs may present a fast and attractive strategy with known safety, characteristics, and dosage used. However, they are not specific and targeted. Therefore, several drugs have been investigated for their efficacy and safety in the treatment of COVID-19; most of them are undergoing clinical trials. This article summarizes clinical investigations of potential therapeutic drugs used as COVID-19 therapy. Subsequently, it prepares a pattern of results and therapeutic targets to help further experiment designs. We have investigated drugs as classified in the following three groups; 1) The drugs which computationally showed effectiveness (in silico) but needed further lab confirmations; 2) Emetine, Teicoplanin, and Nelfinavir have shown effectiveness in vitro; 3) The drugs currently under clinical trial.

Ligament Reconstruction of Traumatic Pure Dislocation of Carpometacarpal Joint of the Thumb: A Series of Acute and Chronic Cases.

Background Traumatic instability of carpometacarpal (CMC) joint of the thumb without a fracture (pure dislocation of CMC joint) is an uncommon injury, and a universally accepted protocol has not yet been developed for its management. Here, we aim to evaluate the outcome of this injury managed with ligament reconstruction technique, in a series of acute and chronic injuries. Patients and Methods Total nine patients (six acute and three chronic) with pure dislocation of CMC joint who underwent ligament reconstruction surgery were included in this retrospective study. Outcome measures included disabilities of the arm, shoulder, and hand (quick-DASH) questionnaire; visual analog scale (VAS) scoring system; patient-rated wrist/hand evaluation (PRWHE) system; pinch and grip strength; and Kapandji thumb opposition scores. Results The patients' mean age was 32.55 ± 11.4 years. Their mean follow-up period was 27 ± 12.8 months. The mean postoperative pinch and grip strength was equivalent to 91.5% and 108% of the contralateral hand, respectively. The mean Quick-DASH score was 14.7 ± 19.4. The mean PRWHE score was 18.7 ± 22.4. The mean VAS was 1.1 ± 1.5. The mean Kapandji score was 8.3 ± 1.4. The pinch and grip strength were considerably superior in acute injuries. Degenerative changes were seen in all joints at the latest follow-up. None of our patients needed a revision surgery. Conclusion Ligament reconstruction method could result in favorable outcome in the management of pure dislocation of CMC joint. However, delayed surgery of this injury might adversely affect the outcome measures.

Designing a chimeric subunit vaccine for influenza virus, based on HA2, M2e and CTxB: a bioinformatics study.

BACKGROUND: Type A influenza viruses are contagious and even life-threatening if left untreated. So far, no broadly protective vaccine is available due to rapid antigenic changes and emergence of new subtypes of influenza virus. In this study, we exploited bioinformatics tools in order to design a subunit chimeric vaccine from the antigenic and highly conserved regions of HA and M2 proteins of H7N9 subtype of influenza virus. We used mucosal adjuvant candidates, including CTxB, STxB, ASP-1, and LTB to stimulate mucosal immunity and analyzed the combination of HA2, M2e, and the adjuvant. Furthermore, to improve the antigen function and to maintain their three-dimensional structure, 12 different linkers including six rigid linkers and six flexible linkers were used. The 3D structure model was generated using a combination of homology and ab initio modeling methods and the molecular dynamics of the model were analyzed, either. RESULTS: Analysis of different adjuvants showed that using CtxB as an adjuvant, results in higher overall vaccine stability and higher half-life among four adjuvant candidates. Fusion of antigens and the CTxB in the form of M2e-linker-CTxB-linker-HA2 has the most stability and half life compared to other combination forms. Furthermore, the KPKPKP rigid linker showed the best result for this candidate vaccine among 12 analyzed linkers. The changes in the vaccine 3D structure made by linker insertion found to be negligible, however, although small, the linker insertion between the antigens causes the structure to change slightly. Eventually, using predictive tools such as Ellipro, NetMHCpan I and II, CD4episcore, CTLpred, BepiPred and other epitope analyzing tools, we analyzed the conformational and linear epitopes of the vaccine. The solubility, proteasome cleavage sites, peptidase and potential chemical cutters, codon optimization, post translational modification were also carried out on the final vaccine. CONCLUSIONS: It is concluded that M2e-Linker-CTxB-Linker-HA2 combination of chimeric vaccine retains its 3D structure and antigenicity when KPKPKP used as linker and CTxB used as adjuvant.

Designer Exosomes: A New Platform for Biotechnology Therapeutics.

Desirable features of exosomes have made them a suitable manipulative platform for biomedical applications, including targeted drug delivery, gene therapy, cancer diagnosis and therapy, development of vaccines, and tissue regeneration. Although natural exosomes have various potentials, their clinical application is associated with some inherent limitations. Recently, these limitations inspired various attempts to engineer exosomes and develop designer exosomes. Mostly, designer exosomes are being developed to overcome the natural limitations of exosomes for targeted delivery of drugs and functional molecules to wounds, neurons, and the cardiovascular system for healing of damage. In this review, we summarize the possible improvements of natural exosomes by means of two main approaches: parental cell-based or pre-isolation exosome engineering and direct or post-isolation exosome engineering. Parental cell-based engineering methods use genetic engineering for loading of therapeutic molecules into the lumen or displaying them on the surface of exosomes. On the other hand, the post-isolation exosome engineering approach uses several chemical and mechanical methods including click chemistry, cloaking, bio-conjugation, sonication, extrusion, and electroporation. This review focuses on the latest research, mostly aimed at the development of designer exosomes using parental cell-based engineering and their application in cancer treatment and regenerative medicine.