COVID-19 outbreak caused by SARS-CoV-2 created an unprecedented health crisis since there is no vaccine for this novel virus. Therefore, SARS-CoV-2 vaccines have become crucial for reducing morbidity and mortality. In this study, in vitro and in vivo safety and efficacy analyzes of lyophilized vaccine candidates inactivated by gamma-irradiation were performed. The candidate vaccines in this study were OZG-3861 version 1 (V1), an inactivated SARS-CoV-2 virus vaccine, and SK-01 version 1 (V1), a GM-CSF adjuvant added vaccine. The candidate vaccines were applied intradermally to BALB/c mice to assess toxicity and immunogenicity. Preliminary results in vaccinated mice are reported in this study. Especially, the vaccine models containing GM-CSF caused significant antibody production with neutralization capacity in absence of the antibody-dependent enhancement feature, when considered in terms of T and B cell responses. Another important finding was that the presence of adjuvant was more important in T cell in comparison with B cell response. Vaccinated mice showed T cell response upon restimulation with whole inactivated SARS-CoV-2 or peptide pool. This study shows that the vaccines are effective and leads us to start the challenge test to investigate the gamma-irradiated inactivated vaccine candidates for infective SARS-CoV-2 virus in humanized ACE2+ mice.

The SARS-CoV-2 virus caused the most severe pandemic around the world, and vaccine development for urgent use became a crucial issue. Inactivated virus formulated vaccines such as Hepatitis A, oral polio vaccine, and smallpox proved to be reliable approaches for immunization for prolonged periods. During the pandemic, we produced an inactivated SARS-CoV-2 vaccine candidate, having the advantages of being manufactured rapidly and tested easily in comparison with recombinant vaccines. In this study, an inactivated virus vaccine that includes a gamma irradiation process for the inactivation as an alternative to classical chemical inactivation methods so that there is no extra purification required has been optimized. The vaccine candidate (OZG-38.61.3) was then applied in mice by employing the intradermal route, which decreased the requirement of a higher concentration of inactivated virus for proper immunization, unlike most of the classical inactivated vaccine treatments. Hence, the novelty of our vaccine candidate (OZG-38.61.3) is that it is a non-adjuvant added, gamma-irradiated, and intradermally applied inactive viral vaccine. Efficiency and safety dose (either 10 ¹³ or 10 ¹⁴ viral copy per dose) of OZG-38.61.3 was initially determined in Balb/c mice. This was followed by testing the immunogenicity and protective efficacy of OZG-38.61.3. Human ACE2-encoding transgenic mice were immunized and then infected with a dose of infective SARS-CoV-2 virus for the challenge test. Findings of this study show that vaccinated mice have lower SARS-CoV-2 viral copy number in oropharyngeal specimens along with humoral and cellular immune responses against the SARS-CoV-2, including the neutralizing antibodies similar to those shown in Balb/c mice without substantial toxicity. Subsequently, plans are being made for the commencement of Phase 1 clinical trial of the OZG-38.61.3 vaccine for the COVID-19 pandemic.

Aim: Duchenne Muscular Dystrophy (DMD) results in a deficiency of dystrophin expression in patient muscle fibers, leading to progressive muscle degeneration. Treatment of DMD has undertaken current transformation with the advancement of novel gene therapy and molecular biology techniques, which are secure, well-tolerated, and effective therapeutic approaches. Introduction: DMD gene therapies have mainly focused on young DMD patients as in vivo animal model trials have been performed in 0–1-month DMD mice. However, it has not yet been answered how micro-dystrophin encoding lentiviral treatment affects Dystrophin expression and DMD symptoms in 10-month mdx mice. Methods: We planned to integrate the micro-Dystrophin gene sequence into the muscle cells by viral transfer, using micro-Dystrophin-encoding lentivirus to reduce the dystrophic pathology in late-stage dmd mice. The histopathological and physiological-functional regeneration activities of the lentiviralmicro- Dystrophin gene therapy methods were compared, along with changes in temporal Dystrophin expression and their functionality, toxicity, and gene expression level. Results: Here, we showed that the micro-dystrophin transgene transfers intramuscularly and intraperitoneally in late-stage dmd-mdx-4cv mice restored dystrophin expression in the skeletal and cardiac muscle (p <0.001). Furthermore, motor performance analysis, including hanging and tracking tests, improved statistically significantly after the treatment (p <0.05). Conclusion: Consequently, this study suggests that patients in the late stages of muscular dystrophy can benefit from lentiviral micro-dystrophin gene therapies to present an improvement in dystrophic muscle pathology.

Objective: This study aimed to compare the effects of human umbilical cord mesenchymal stem cells (hUCMSCs), amniotic fluid (AF), and a combination of both on the uterus and ovaries in a rat model of abdominal adhesions.Material and Methods: This study was designed as a controlled study. Four groups, each consisting of six rats, were randomly formed. One group was designated as the control (CNT). hUCMSCs -applied (hUCSC), AF-applied (AMN), and a combination of both (hUCSC + AMN) were the experimental groups. All rats were given intraperitoneal talc powder to create adhesions. After 21 days, animals in experimental groups were further treated with hUCMSC, AF or a combination of these.Results: There was a statistically significant difference in primordial follicle count, endometrial gland number, and endometrial blood vessel count (p<0.05). AMN provided the best results in the endometrial vessel and primordial follicle count. The average endometrial gland count in AMN and hUCSC + AMN was similarly higher than CNT and hUCSC alone.Conclusion: There were significantly higher for counts for endometrial glands, endometrial blood vessels, and primordial follicles in the hUCSC, AMN and hUCSC + AMN groups compared to controls. Animals in the AMN group had the best result for endometrial vessel and highest primordial follicle count. (J Turk Ger Gynecol Assoc 2022; 23: 154-66)

Objective: The aim of this study was to provide anatomic considerations in the first metatarsophalangeal joint (FMPJ) innervation and to evaluate the feasibility of the denervation surgery in the treatment of hallux rigidus. Methods: In this cadaveric study, 14 fresh frozen cadaveric transtibial amputation specimens was used. For nerve dissection, dorsal and plantar longitudinal incision centered over the FMPJ were performed. Deep peroneal and dorsomedial cutaneous nerves were dissected in the dorsal aspect of the joint. Medial plantar nerve branches, medial and lateral hallucal nerves, were dissected in the plantar aspect of the joint. The presence, number, and location of articular branches to the FMPJ capsule were recorded. Dorsal and plantar incision length for proper dissection were also recorded. Results: Nerve dissection of the 14 specimens revealed the following number of articular branches from the relevant nerves: 14 from dorsomedial cutaneous nerves, 11 from deep peroneal nerves, 6 from medial hallucal nerve, and 5 from lateral hallucal nerve. Dorsal incision mean length was 60.53 (range, 42.48˗85.12) mm, and the plantar incision mean length was 88.08 (range, 77.32˗111.21) mm. Conclusion: Evidence from this study has shown that partial dorsal denervation of the FMPJ may be a technically feasible procedure along with the presence of superficially easily dissected nerves with relatively small incision. Level of Evidence: Level 5 Cite this article as: Çatal B, Keskinbora M, Keskinöz EN, et al. Is denervation surgery possible in the treatment of hallux rigidus? An anatomic study of cadaveric specimens. Acta Orthop Traumatol Turc 2021; 55(4): 327–331.

PurposeThis study aimed to evaluate whether cilostazol (phosphodiesterase III inhibitor) could enhance the healing of Achilles tendon ruptures in rats.Materials and methodsThe Achilles tendons of 24 healthy male adult rats were incised and repaired. The rats were randomly allocated to cilostazol and control groups. The cilostazol group received daily intragastric administration of 50 mg/kg cilostazol for 28 days, while the control group did not receive any medication. The rats were sacrificed on the 30th day, and the Achilles tendon was evaluated for biomechanical properties, histopathological characteristics, and immunohistochemical analysis.ResultsAll rats completed the experiment. The Movin sum score of the control group was significantly higher (p = 0.008) than that of the cilostazol group, with means of 11 +/- 0.63 and 7.50 +/- 1.15, respectively. Similarly, the mean Bonar score was significantly higher (p = 0.026) in the control group compared to the cilostazol group (8.33 +/- 1.50 vs. 5.5 +/- 0.54, respectively). Moreover, the Type I/Type III Collagen ratio was notably higher (p = 0.016) in the cilostazol group (52.2 +/- 8.4) than in the control group (34.6 +/- 10.2). The load to failure was substantially higher in the cilostazol group than in the control group (p = 0.034), suggesting that the tendons in the cilostazol group were stronger and exhibited greater resistance to failure.ConclusionsThe results of this study suggest that cilostazol treatment significantly improves the biomechanical and histopathological parameters of the healing Achilles tendon in rats. Cilostazol might be a valuable supplementary therapy in treating Achilles tendon ruptures in humans. Additional clinical studies are, however, required to verify these outcomes.