Predictors of health-related quality of life after total knee arthroplasty: a case-control study.

Total knee arthroplasty (TKA) improves patients' Health-related quality of life (HRQoL) compared to before surgery. However, based on our knowledge, the improvement in HRQoL after TKA, which depends on various factors, has yet to be investigated compared to healthy people. This study aimed to evaluate the HRQoL of patients compared to healthy people and the factors affecting the HRQoL after TKA. In this matched case-control study (1002 participants), HRQoL in 501 patients who underwent TKA between 2015 and 2022 at Shafa Yahyainan Hospital affiliated with Iran University of Medical Sciences were compared with 501 healthy controls. HRQoL was evaluated in two parts (before compared to 12 months after TKA and 12 months after TKA compared to the healthy population). The 36-item short-form health survey (SF-36) was used to evaluate HRQoL 12 months after surgery. The influencing factors on HRQoL were evaluated by multivariate logistic regression analysis. No significant difference was observed in the demographic characteristics of the participants in the two groups. The mean overall SF-36 score, 12 months after surgery, significantly improved compared to before surgery (64.21 ± 22.2 vs. 37.55 ± 15.13, p:0.001). The mean total score of SF-36 was statistically similar between the case and control groups (64.21 ± 22.2 VS 72.53 ± 25.3). The multivariate analysis showed that sex, BMI, number of comorbidities, postoperative compliance, and complications were significantly related to the decrease in patients' HRQoL (P < 0.001).TKA can improve the HRQoL except for two subscales of happiness/vitality and physical performance, similar to the healthy population. Female gender, obesity and overweight, comorbidity, bilateral TKA, non-adherence to postoperative physiotherapy, and complications were associated with decreased HRQoL.

Evaluation of ChatGPT's responses to information needs and information seeking of dementia patients.

Many people in the advanced stages of dementia require full-time caregivers, most of whom are family members who provide informal (non-specialized) care. It is important to provide these caregivers with high-quality information to help them understand and manage the symptoms and behaviors of dementia patients. This study aims to evaluate ChatGPT, a chatbot built using the Generative Pre-trained Transformer (GPT) large language model, in responding to information needs and information seeking of such informal caregivers. We identified the information needs of dementia patients based on the relevant literature (22 articles were selected from 2442 retrieved articles). From this analysis, we created a list of 31 items that describe these information needs, and used them to formulate 118 relevant questions. We then asked these questions to ChatGPT and investigated its responses. In the next phase, we asked 15 informal and 15 formal dementia-patient caregivers to analyze and evaluate these ChatGPT responses, using both quantitative (questionnaire) and qualitative (interview) approaches. In the interviews conducted, informal caregivers were more positive towards the use of ChatGPT to obtain non-specialized information about dementia compared to formal caregivers. However, ChatGPT struggled to provide satisfactory responses to more specialized (clinical) inquiries. In the questionnaire study, informal caregivers gave higher ratings to ChatGPT's responsiveness on the 31 items describing information needs, giving an overall mean score of 3.77 (SD 0.98) out of 5; the mean score among formal caregivers was 3.13 (SD 0.65), indicating that formal caregivers showed less trust in ChatGPT's responses compared to informal caregivers. ChatGPT's responses to non-clinical information needs related to dementia patients were generally satisfactory at this stage. As this tool is still under heavy development, it holds promise for providing even higher-quality information in response to information needs, particularly when developed in collaboration with healthcare professionals. Thus, large language models such as ChatGPT can serve as valuable sources of information for informal caregivers, although they may not fully meet the needs of formal caregivers who seek specialized (clinical) answers. Nevertheless, even in its current state, ChatGPT was able to provide responses to some of the clinical questions related to dementia that were asked.

Evaluation of the Newcastle disease virus genotype VII-mismatched vaccines in SPF chickens: A challenge efficacy study.

Newcastle disease virus (NDV) strains, while falling under a single serotype, are classified into distinct genotypes. Genotype VII virulent NDVs pose a significant threat to poultry due to their association with high mortality rates and economic losses. This study aimed to evaluate the efficacy of three commercial live vaccines based on genotype II against genotype VII virulent NDV (vNDV) in specific pathogen-free (SPF) chickens. Forty one-day-old chickens were randomly divided into four groups (n = 10) and inoculated with one dose of each ND pneumotropic vaccine-B1, Clone.12IR, and La Sota-or received phosphate-buffered saline (PBS) as a control at eight days of age via eye drop. At 28 days of age (20th post-vaccination days), chickens were intramuscularly challenged with genotype VII virulent NDV (≥ 105 LD50). Serum samples were collected at 28 days of age (challenge day), 7 and 14 post-challenge days to measure NDV antibodies via the hemagglutination inhibition (HI) test. Cloacal and oropharyngeal swabs were taken on the 3rd, 5th, 7th, and 10th post-challenge days to evaluate virus shedding. Vaccinated groups exhibited significantly higher antibody titers and greater protection levels compared to the control group (P≤ 0.001). While HI antibody titer was not different at 28 and 35 days of age between vaccinated chickens, the Clone.12IR groups showed higher HI antibody titer compared to B1 at day 42 of age (9.43 vs. 7.42; P≤ 0.002). La Sota and Clone.12IR vaccines demonstrated superior protection against mortality compared to the B1 vaccine (90 %, 80% vs. 60 %, respectively) with 6.0 and 2.67 odds ratio of survivability. All three mismatched vaccines effectively curbed the shedding of virulent genotype VII NDV, with 0 % to 11 % positive cloacal samples up to the 3rd post-challenge day. These findings demonstrate that in the experimental setting, the administration of mismatched ND vaccines, particularly La Sota and Clone.12IR, confer protection against genotype VII virulent NDV and control viral shedding, which can help to develop effective vaccination strategies to mitigate the impact of vNDV outbreaks in the poultry farms.

Recent Advances in the Role of Different Nanoparticles in the Various Biosensors for the Detection of the Chikungunya Virus.

Humans contract the Chikungunya virus (CHIKV), an alphavirus transmitted by mosquitoes that induces acute and chronic musculoskeletal discomfort and fever. Millions of cases of the disease have been attributed to CHIKV in the Indian Ocean region since 2004, and the virus has since spread to Europe, the Middle East, and the Pacific. The exponential proliferation of CHIKV in recent times underscores the critical nature of implementing preventative measures and exploring potential control strategies. The principal laboratory test employed to diagnose infection in serum samples collected over six days after the onset of symptoms is the detection of CHIKV or viral RNA. Although two commercially available real-time reverse transcription-polymerase chain reaction products exist, data on their validity are limited. A diagnostic instrument that is rapid, sensitive, specific, and cost-effective is, therefore an absolute necessity, particularly in developing nations. Biosensors have demonstrated considerable potential in the realm of pathogen detection. The rapid and sensitive detection of viruses has been facilitated by the development of numerous types of biosensors, including affinity-based nano-biosensors, graphene affinity-based biosensors, optical nano-biosensors, surface Plasmon Resonance-based optical nano-biosensors, and electrochemical nano-biosensors. Furthermore, the utilization of nanomaterials for signal extension, including but not limited to gold and silver nanoparticles, quantum dots, and iron oxide NPs, has enhanced the precision and sensitivity of biosensors. The developed innovative diagnostic method is time-efficient, precise, and economical; it can be implemented as a point-of-care device. The technique may be implemented in diagnostic laboratories and hospitals to identify patients infected with CHIKV. Throughout this article, we have examined a multitude of CHIKV nano-biosensors and their respective properties. Following a discussion of representative nanotechnologies for biosensors, numerous NPs-assisted CHIKV nano-biosensors are summarized in this article. As a result, we anticipate that this review will furnish a significant foundation for advancing innovative CHIKV nano-biosensors.

Smart city healthcare delivery innovations: a systematic review of essential technologies and indicators for developing nations.

BACKGROUND: In recent times, the concept of smart cities has gained remarkable traction globally, driven by the increasing interest in employing technology to address various urban challenges, particularly in the healthcare domain. Smart cities are proving to be transformative, utilizing an extensive array of technological tools and processes to improve healthcare accessibility, optimize patient outcomes, reduce costs, and enhance overall efficiency. METHODS: This article delves into the profound impact of smart cities on the healthcare landscape and discusses its potential implications for the future of healthcare delivery. Moreover, the study explores the necessary infrastructure required for developing countries to establish smart cities capable of providing intelligent health and care services. To ensure a comprehensive analysis, we employed a well-structured search strategy across esteemed databases, including PubMed, OVID, EMBASE, Web of Science, and Scopus. The search scope encompassed articles published up to November 2022, resulting in a meticulous review of 22 relevant articles. RESULTS: Our findings provide compelling evidence of the pivotal role that smart city technology plays in elevating healthcare delivery, forging a path towards improved accessibility, efficiency, and quality of care for communities worldwide. By harnessing the power of data analytics, Internet of Things (IoT) sensors, and mobile applications, smart cities are driving real-time health monitoring, early disease detection, and personalized treatment approaches. CONCLUSION: Smart cities possess the transformative potential to reshape healthcare practices, providing developing nations with invaluable opportunities to establish intelligent and adaptable healthcare systems customized to their distinct requirements and limitations. Moreover, the implementation of smart healthcare systems in developing nations can lead to enhanced healthcare accessibility and affordability, as the integration of technology can optimize resource allocation and improve the overall efficiency of healthcare services. It also may help alleviate the burden on overburdened healthcare facilities by streamlining patient care processes and reducing wait times, ensuring that medical attention reaches those in need more swiftly.

Frequency of B-Cell Subpopulations in Low Responders in Comparison with High Responders to Hepatitis B Vaccine Among Health Care Workers.

Vaccination is the most effective way to prevent Hepatitis B (HB) infection. The goal of vaccination is to induce immunological memory. Hence, determining the frequency of memory B-cell (MBC) subsets is an important indicator of vaccine efficacy. This study aimed to evaluate the frequency of different B-cell subpopulations and the expression of PD-1 on B-cell subsets in low responders (LR) and high responders (HR) to HB vaccine. According to our findings, the expression level of PD-1 was significantly higher on atypical MBC (atMBC) than that of naive B cell and classical MBC (cMBC) in LR and HR groups. Moreover, cMBCs had a significant higher PD-1 expression than naive B cells in LR group. No significant differences were found in the frequency of various B-cell subpopulations and the expression level of PD-1 on B-cell subsets between LR and HR groups. We observed a negative correlation between age and HBsAb titer and a positive correlation between age and PD-1 expression level on cMBC in LR group. It can be concluded that inadequate specific memory B-cell response, rather than total memory B-cell deficiency, may be implicated in low responsive rate to HB vaccine in healthy individuals.

Cartilage regeneration and inflammation modulation in knee osteoarthritis following injection of allogeneic adipose-derived mesenchymal stromal cells: a phase II, triple-blinded, placebo controlled, randomized trial.

BACKGROUND: Intra-articular injection of mesenchymal stromal cells (MSCs) with immunomodulatory features and their paracrine secretion of regenerative factors proposed a noninvasive therapeutic modality for cartilage regeneration in knee osteoarthritis (KOA). METHODS: Total number of 40 patients with KOA enrolled in two groups. Twenty patients received intra-articular injection of 100 × 106 allogeneic adipose-derived mesenchymal stromal cells (AD-MSCs), and 20 patients as control group received placebo (normal saline). Questionnaire-based measurements, certain serum biomarkers, and some cell surface markers were evaluated for 1 year. Magnetic resonance imaging (MRI) before and 1 year after injection was performed to measure possible changes in the articular cartilage. RESULTS: Forty patients allocated including 4 men (10%) and 36 women (90%) with average age of 56.1 ± 7.2 years in control group and 52.8 ± 7.5 years in AD-MSCs group. Four patients (two patients from AD-MSCs group and two patients from the control group) excluded during the study. Clinical outcome measures showed improvement in AD-MSCs group. Hyaluronic acid and cartilage oligomeric matrix protein levels in blood serum decreased significantly in patients who received AD-MSCs (P < 0.05). Although IL-10 level significantly increased after 1 week (P < 0.05), the serum level of inflammatory markers dramatically decreased after 3 months (P < 0.001). Expressions of CD3, CD4, and CD8 have a decreasing trend during 6-month follow-up (P < 0.05), (P < 0.001), and (P < 0.001), respectively. However, the number of CD25+ cells increased remarkably in the treatment group 3 months after intervention (P < 0.005). MRI findings showed a slight increase in the thickness of tibial and femoral articular cartilages in AD-MSCs group. The changes were significant in the medial posterior and medial anterior areas of ​​the tibia with P < 0.01 and P < 0.05, respectively. CONCLUSION: Inter-articular injection of AD-MSCs in patients with KOA is safe. Laboratory data, MRI findings, and clinical examination of patients at different time points showed notable articular cartilage regeneration and significant improvement in the treatment group. TRIAL REGISTRATION: Iranian registry of clinical trials (IRCT, https://en.irct.ir/trial/46 ), IRCT20080728001031N23. Registered 24 April 2018.

The most prominent modulated Annexins during parasitic infections.

Annexins (ANXs) exert different functions in cell biological and pathological processes and are thus known as double or multi-faceted proteins. These sophisticated proteins might express on both parasite structure and secretion and in parasite-infected host cells. In addition to the characterization of these pivotal proteins, describing their mechanism of action can be also fruitful in recognizing their roles in the pathogenesis of parasitic infections. Accordingly, this study presents the most prominent ANXs thus far identified and their relevant functions in parasites and infected host cells during pathogenesis, especially in the most important intracellular protozoan parasitic infections including leishmaniasis, toxoplasmosis, malaria and trypanosomiasis. The data provided in this study demonstrate that the helminth parasites most probably express and secret ANXs to develop pathogenesis while the modulation of the host-ANXs could be employed as a crucial strategy by intracellular protozoan parasites. Moreover, such data highlight that the use of analogs of both parasite and host ANX peptides (which mimic or regulate ANXs physiological functions through various strategies) might suggest novel therapeutic insights into the treatment of parasitic infections. Furthermore, due to the prominent immunoregulatory activities of ANXs during most parasitic infections and the expression levels of these proteins in some parasitic infected tissues, such multifunctional proteins might be also potentially relevant as vaccine and diagnostic biomarkers. We also suggest some prospects and insights that could be useful and applicable to form the basis of future experimental studies.

Functional outcomes and quality of life after surgically treated tibial plateau fractures.

BACKGROUND: Tibial plateau fractures (TPF) are uncommon and challenging for orthopedic surgeons with controversial reported outcomes. In this study, we aimed to evaluate the functional outcomes and quality of life (QOL) of patients with surgically treated TPF. METHODS: A total of 80 consecutive patients and 82 controls participated in this case control study. The patients were all surgically treated in our tertiary center from April 2012 to April 2020. The functional outcome was evaluated using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) scale. Moreover, we used the Short Form 36 health survey (SF-36) health survey to evaluate the QOL. RESULTS: No significant difference was observed in the overall mean SF-36 score in the two groups. We found a significant positive correlation between the scores of the SF-36 and WOMAC questionnaires (r = 0.642, p < 0.001) and between the ROM and the WOMAC questionnaire score (r = 0.478, p < 0.001). Further, ROM and SF-36 showed a weak positive correlation (r = 0.248, p = 0.026). Age had a weak negative correlation with the pain subscale of SF-36 (r = - 0.255, p = 0.22), even though it was not correlated with the total score or other subscales (p > 0.05). CONCLUSION: QoL after TPF is not significantly different from that of a matched control group. Also, neither age nor BMI correlates with the QoL and functional outcome.

In vitro-Generated MDSCs Reduce the Pregnancy Complications in an Abortion-Prone Murine Model.

Recurrent spontaneous abortion (RSA) is one of the major pregnancy-related complications. The roles of different immune cells have been studied in pregnancy complications. The current study aimed to investigate myeloid-derived suppressor cells (MDSCs) in a murine abortion model and introduce a therapeutic approach by using in vitro-generated MDSCs in this model. CBA/J × DBA/2 (abortion prone) and CBA/J × Balb/C (normal pregnancy) mice were used. The frequency of granulocytic MDSCs, monocytic MDSCs, and Tregs was checked in the bone marrow and uteroplacental tissue of mice on three gestational days (gd9.5, gd13.5, and gd17.5) using the flow cytometry approach. MDSCs were generated in vitro from bone marrow-isolated cells using GM-CSF and IL-6 cytokines. Abortion-prone mice were injected intravenously with in vitro-generated MDSCs at gd0.5, and pregnancy outcomes were recorded in treated mice. The frequency of G-MDSCs and M-MDSCs in the bone marrow of abortion-prone mice was decreased at gd9.5 (p = 0.026 and p = 0.05, respectively). In uteroplacental tissue, the frequency of G-MDSCs was significantly lower at gd9.5 and gd13.5 (p = 0.001, p = 0.029, respectively), while M-MDSCs only showed decreased number at gd9.5 (p = 0.05) in abortion-prone mice. Injection of in vitro-generated MDSCs resulted in the increased fetus and placenta weights (p = 0.049 and p = 0.012, respectively) but showed no effect on the number of live fetuses and abortion rate. The reduced frequency of both G-MDSCs and M-MDSCs in the bone marrow and at the feto-maternal interface is associated with pregnancy complications. In vitro-generated MDSCs could be considered as a potential approach to reduce these complications.

The Defensive Interactions of Prominent Infectious Protozoan Parasites: The Host's Complement System.

The complement system exerts crucial functions both in innate immune responses and adaptive humoral immunity. This pivotal system plays a major role dealing with pathogen invasions including protozoan parasites. Different pathogens including parasites have developed sophisticated strategies to defend themselves against complement killing. Some of these strategies include the employment, mimicking or inhibition of host's complement regulatory proteins, leading to complement evasion. Therefore, parasites are proven to use the manipulation of the complement system to assist them during infection and persistence. Herein, we attempt to study the interaction´s mechanisms of some prominent infectious protozoan parasites including Plasmodium, Toxoplasma, Trypanosoma, and Leishmania dealing with the complement system. Moreover, several crucial proteins that are expressed, recruited or hijacked by parasites and are involved in the modulation of the host´s complement system are selected and their role for efficient complement killing or lysis evasion is discussed. In addition, parasite's complement regulatory proteins appear as plausible therapeutic and vaccine targets in protozoan parasitic infections. Accordingly, we also suggest some perspectives and insights useful in guiding future investigations.

The frequency of CD4+ and CD8+ circulating T stem cell memory in type 1 diabetes.

INTRODUCTION: The frequencies and functions of T stem cell memory (TSCM) subsets vary in autoimmune diseases. We evaluated the frequencies of CD4+ and CD8+ TSCM subsets as well as their PD-1 expression levels in patients with T1D. METHODS: Blood samples were collected from new case (NC) (n = 15), and long-term (LT) (n = 15) groups and healthy controls (n = 15). Five subsets of T cells including TCM(CD4+ /CD8+ CCR7+ CD45RO+ CD95+ ), TCMhi (CD4+ /CD8+ CCR7+ CD45ROhi CD95+ ), TEM(CD4+ /CD8+ CCR7- CD45RO+ CD95+ ), TSCM(CD4+ /CD8+ CCR7+ CD45RO- CD95+ ), and T naive (CD4+ /CD8+ CCR7+ CD45RO- CD95- ) were detected by flow-cytometry. RESULTS: The frequency of CD4+ TSCM was higher in NC patients than LT patients and controls (p < .0001 and p = .0086, respectively). A higher percentage of the CD8+ T naive cells was shown in NC patients as compared with LT and healthy individuals (p = .0003 and p = .0002, respectively). An increased level of PD-1 expression was observed on the CD4+ TCM and TCMhi cells in LT patients as compared with healthy controls (p = .0037 and p = .0145, respectively). Also, the higher PD-1 expression was observed on the CD8+ TCM and TCMhi in NC and LT patients as compared with controls (p = .0068 and p < .0001; p = .0012 and p = .0012, respectively). CONCLUSION: Considering TSCMs' capacities to generate all memory and effector T cells, our results may suggest a potential association between the increased frequencies of TSCMs and T1D progression.

Development of a Mobile App for Self-Care Against COVID-19 Using the Analysis, Design, Development, Implementation, and Evaluation (ADDIE) Model: Methodological Study.

BACKGROUND: Mobile apps have been shown to play an important role in the management, care, and prevention of infectious diseases. Thus, skills for self-care-one of the most effective ways to prevent illness-can be improved through mobile health apps. OBJECTIVE: This study aimed to design, develop, and evaluate an educational mobile-based self-care app in order to help the self-prevention of COVID-19 in underdeveloped countries. We intended the app to be easy to use, quick, and inexpensive. METHODS: In 2020 and 2021, we conducted a methodological study. Using the ADDIE (analysis, design, development, implementation, and evaluation) educational model, we developed a self-care management mobile app. According to the ADDIE model, an effective training and performance support tool is built through the 5 phases that comprise its name. There were 27 participants who conducted 2 evaluations of the mobile app's usability and impact using the mobile health app usability and self-care inventory scales. The study design included pre- and posttesting. RESULTS: An Android app called MyShield was developed. The results of pre- and posttests showed that on a scale from 0 to 5, MyShield scored a performance average of 4.17 in the physical health dimension and an average of 3.88 in the mental well-being dimension, thereby showing positive effects on self-care skills. MyShield scored highly on the "interface and satisfaction," "ease of use," and "usefulness" components. CONCLUSIONS: MyShield facilitates learning self-care skills at home, even during quarantine, increasing acquisition of information. Given its low development cost and the ADDIE educational design on which it is based, the app can be helpful in underdeveloped countries. Thus, low-income countries-often lacking other tools-can use the app as an effective tool for fighting COVID-19, if it becomes a standard mobile app recommended by the government.

Clinical and laboratory findings following transplantation of allogeneic adipose-derived mesenchymal stromal cells in knee osteoarthritis, a brief report.

BACKGROUND: Mesenchymal stromal cells (MSCs) injection has been proposed as an innovative treatment for knee osteoarthritis (KOA). Since, allogeneic MSCs can be available as off-the-shelf products, they are preferable in regenerative medicine. Among different sources for MSCs, adipose-derived MSCs (AD-MSCs) appear to be more available. METHODS: Three patients with KOA were enrolled in this study. A total number of 100 × 106 AD-MSCs was injected intra-articularly, per affected knee. They were followed up for 6 months by the assessment of clinical outcomes, magnetic resonance imaging (MRI), and serum inflammatory biomarkers. RESULTS: The primary outcome of this study was safety and feasibility of allogeneic AD-MSCs injection during the 6 months follow-up. Fortunately, no serious adverse events (SAEs) were reported. Assessment of secondary outcomes of visual analogue scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and knee osteoarthritis outcome score (KOOS) indicated improvement in all patients. Comparison between baseline and endpoint findings of MRI demonstrated a slight improvement in two patients. In addition, decrease in serum cartilage oligomeric matrix protein (COMP) and hyaluronic acid (HA) indicated the possibility of reduced cartilage degeneration. Moreover, quantification of serum interleukin-10 (IL-10) and interleukin-6 (IL-6) levels indicated that the host immune system immunomodulated after infusion of AD-MSCs. CONCLUSION: Intra-articular injection of AD-MSCs is safe and could be effective in cartilage regeneration in KOA. Preliminary assessment after six-month follow-up suggests the potential efficacy of this intervention which would need to be confirmed in randomized controlled trials on a larger population. TRIAL REGISTRATION: This study was registered in the Iranian registry of clinical trials (https://en.irct.ir/trial/46) in 24 April 2018 with identifier IRCT20080728001031N23.

Cardiovascular protective effects of PPARγ agonists in hypothyroid rats: protection against oxidative stress.

Hypothyroidism disturbs redox homeostasis and takes part in cardiovascular system dysfunction. Considering antioxidant and cardio-protective effects of PPAR-γ agonists including pioglitazone (POG) and rosiglitazone (RSG), the present study was aimed to determine the effect of POG or RSG on oxidants and antioxidants indexes in the heart and aorta tissues of Propylthiouracil (PTU)-induced hypothyroid rats. MATERIALS AND METHODS: The animals were divided into six groups: (1) Control; (2) propylthiouracil (PTU), (3) PTU-POG 10, (4) PTU-POG 20, (5) PTU-RSG 2, and (6) PTU-RSG 4. Hypothyroidism was induced in rats by giving 0.05% propylthiouracil (PTU) in drinking water for 42 days. The rats of PTU-POG 10 and PTU-POG 20 groups received 10 and 20 mg/kg POG, respectively, besides PTU, and the rats of PTU-RSG 2 and PTU-RSG 4 groups received 2 and 4 mg/kg RSG, respectively, besides PTU. The animals were sacrificed, and the serum of the rats was collected to measure thyroxine level. The heart and aorta tissues were also removed for the measurement of biochemical oxidative stress markers. RESULTS: Hypothyroidism was induced by PTU administration, which was indicated by lower serum thyroxine levels. Hypothyroidism also was accompanied by a decrease of catalase (CAT), superoxide dismutase (SOD) activities, and thiol concentration in the heart and aorta tissues while increased level of malondialdehyde (MDA). Interestingly, administration of POG or RSG dramatically reduced oxidative damage in the heart and aorta, as reflected by a decrease in MDA and increased activities of SOD, CAT, and thiol content. CONCLUSION: The results of this study showed that administration of POG or RSG decreased oxidative damage in the heart and aorta tissues induced by hypothyroidism in rats.

Mining the Proteome of Toxoplasma Parasites Seeking Vaccine and Diagnostic Candidates.

Toxoplasma gondii is a pathogenic protozoan parasite that infects the nucleated cells of warm-blooded hosts leading to an infectious zoonotic disease known as toxoplasmosis. The infection outcomes might be severe and fatal in patients with immunodeficiency, diabetes, and pregnant women and infants. The One Health approach to toxoplasmosis highlights that the health of humans is closely related to the health of animals and our common environment. The presence of drug resistance and side effects, the further improvement of sensitivity and specificity of serodiagnostic tools and the potentiality of vaccine candidates to induce the host immune response are considered as justifiable reasons for the identification of novel targets for the better management of toxoplasmosis. Thus, the identification of new critical proteins in the proteome of Toxoplasma parasites can also be helpful in designing and test more effective drugs, vaccines, and diagnostic tools. Accordingly, in this study we present important proteins found in the proteome of the life cycle-specific stages of Toxoplasma parasites that are potential diagnostic or vaccine candidates. The current study might help to understand the complexity of these parasites and provide a possible source of strategies and biomolecules that can be further evaluated in the pathobiology of Toxoplasma parasites and for diagnostics and vaccine trials against this disease.

Host cell proteins modulated upon Toxoplasma infection identified using proteomic approaches: a molecular rationale.

Toxoplasma gondii is a pathogenic protozoan parasite belonging to the apicomplexan phylum that infects the nucleated cells of warm-blooded hosts leading to an infectious disease known as toxoplasmosis. Apicomplexan parasites such as T. gondii can display different mechanisms to control or manipulate host cells signaling at different levels altering the host subcellular genome and proteome. Indeed, Toxoplasma is able to modulate host cell responses (especially immune responses) during infection to its advantage through both structural and functional changes in the proteome of different infected cells. Consequently, parasites can transform the invaded cells into a suitable environment for its own replication and the induction of infection. Proteomics as an applicable tool can identify such critical proteins involved in pathogen (Toxoplasma)-host cell interactions and consequently clarify the cellular mechanisms that facilitate the entry of pathogens into host cells, and their replication and transmission, as well as the central mechanisms of host defense against pathogens. Accordingly, the current paper reviews several proteins (identified using proteomic approaches) differentially expressed in the proteome of Toxoplasma-infected host cells (macrophages and human foreskin fibroblasts) and tissues (brain and liver) and highlights their plausible functions in the cellular biology of the infected cells. The identification of such modulated proteins and their related cell impact (cell responses/signaling) can provide further information regarding parasite pathogenesis and biology that might lead to a better understanding of therapeutic strategies and novel drug targets.

The tricks for fighting against cancer using CAR NK cells: A review.

Natural killer (NK) cells seem to be the most common innate lymphocyte subtypes, and they're known for their ability to guide anti-tumor and anti-viral responses, making them potentially therapeutic. Since NK cells lack polymorphic clonotypic receptors, they must rely on inhibitory receptors to develop, mature, and distinguish between "self" and "non-self." In the clinic, genetically engineered immune cells expressing a chimeric antigen receptor (CAR) that consists of an extracellular antigen recognizing domain connected to an intracellular signaling domain have gained interest. The U.S. food and drug administration (FDA) approved two CAR-T cells, anti-CD19 CARs, for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL). Nevertheless, CAR-T cell therapy is linked to a series of negative side effects, including fatal cytokine release syndrome (CRS) and tumor lysis syndrome (TLS), as well as a lack of regulatory control. CAR-transduced NK cells (CAR-NK) are thought to have many benefits, including clinical safety, the mechanisms by which they identify cancerous cells, and their abundance in clinical specimens, according to a growing number of studies. In pre-clinical and clinical trials, human primary NK cells and the NK-92 cell line were effectively transduced to express CARs against hematological cancers and solid tumors. Here, it is tried to summarize the development of CAR-NK cells, challenges and coping strategies, as well as managing the challenges and obstacles related to its protection, which promises to eliminate the shortcomings of conventional CARs.

miRNAs in the regulation of mTOR signaling and host immune responses: The case of Leishmania infections.

Micro RNAs (miRNAs), as regulators of gene expression at the post-transcriptional level, can respond to/or interact with cell signaling and affect the pathogenesis of different diseases/infections. The interaction/crosstalk of miRNAs with various cellular signaling networks including mTOR (as a master regulator of signaling relevant to different cellular mechanisms) might lead to the initiation, progression or restriction of certain disease processes. There are numerous studies that have identified the crosstalk between regulatory miRNA expression and the mTOR pathway (or mTOR signaling regulated by miRNAs) in different diseases which has a dual function in pathogenesis. However, the corresponding information in parasitic infections remains scarce. miRNAs have been suggested as specific targets for therapeutic strategies in several disorders such as parasitic infections. Thus, the targeting of miRNAs (as the modulators/regulators of mTOR) by small molecules and RNA-based therapeutics and consequently managing and modulating mTOR signaling and the downstream/related cell signaling/pathways might shed some light on the design of new therapeutic strategies against parasitic diseases, including Leishmaniasis. Accordingly, the present study attempts to highlight the importance of the crosstalk between regulatory miRNAs and mTOR signaling, and to review the relevant insights into parasitic infections by focusing specifically on Leishmania.

Thermoresistant Newcastle disease vaccine effectively protects SPF, native, and commercial chickens in challenge with virulent virus.

BACKGROUND: Due to the more stability and a better homogenecity in immune response, the use of thermoresistant vaccines in different chicken types has been increased. OBJECTIVE: This study aimed to evaluate the efficacy of a newly developed Newcastle disease vaccine (ND.TR.IR) originating from I-2 strain in specific pathogen-free (SPF) and native and broiler chickens. METHODS: Following determination of pathogenicity indices on the candidate seed, three efficacy examinations were conducted. In the first experiment, 120 1-day-old SPF chickens were randomly allocated to six groups and either vaccinated with ND.TR.IR via eye drop at 1, 7, and 21 days of age (V1 , V7 , and V21 ), or considered as non-vaccinated control groups (C1 , C7 , and C21 ). At 20th post-vaccination day, sera hemagglutination inhibition (HI) antibody titres against ND virus (NDV) were measured and then the chickens were challenged by virulent NDV (vNDV). In the second and third experiments, the efficacy of ND.TR.IR vaccine was compared to routine vaccination program (B1 and LaSota) in native and broiler chickens that were vaccinated at 10 and 20 days of age, respectively. The HI antibody titres were measured on 10, 20, 30, and 40 days of age, and also challenge efficacy test with vNDV was conducted on 30 days of age. RESULTS: The studied virus, as a vaccinal seed, complied with the pathogenicity indices of avirulent NDV and molecular identity of I-2 strain. In the efficacy evaluation trials, the vaccinated chickens had higher HI antibody titres against NDV compared with their corresponding control chickens (p < 0.05). Results of the challenge tests indicated 95% and 100% protection against vNDV in native, SPF, and broiler-vaccinated chickens, respectively. CONCLUSIONS: The present findings indicated that administration of ND.TR.IR induced appropriate HI antibody titres against NDV in SPF, native, and broiler chickens associated with good protection in efficacy test.