Investigating the impact of Tocilizumab, Sarilumab, and Anakinra on clinical outcomes in COVID-19: A systematic review and meta-analysis.

Background: Monoclonal antibodies (mAbs) are currently under investigation as a potential therapeutic option for COVID-19. Clinical trials are examining their efficacy in lowering mortality rates and the requirement for mechanical ventilation (MV). It is necessary to conduct a thorough examination of current randomized controlled trials (RCTs) in order to provide more definitive evidence on their effectiveness for COVID-19 patients. This meta-analysis aims to analyze RCT results on the impact of three mAbs (Anakinra, Sarilumab, Tocilizumab) on COVID-19 patient outcomes. Method: The meta-analysis was conducted in accordance with the PRISMA guidelines. Eligible RCTs were conducted to evaluate the effectiveness of three mAbs in treating patients with COVID-19. These trials were identified by searching various databases up to April 1, 2024. In total, this meta-analysis incorporated 19 trials with a total of 8097 patients. Pooled relative risk and studies' heterogeneity were assessed by statistical analysis, which involved the use of fixed effects models and subgroup analysis. Result: The administration of mAbs (Tocilizumab, Sarilumab, and Anakinra) showed various results in the management of COVID-19 patients. While the overall pooled data did not reveal a significant reduction in the need for MV, the study found that the use of mAbs was associated with a decreased risk of clinical worsening (pooled relative risk: 0.75, 95 % CI [0.59, 0.94], p = 0.01) and an increased probability of discharging COVID-19 patients by day 28 or 29 (pooled relative risk: 1.17, 95 % CI [1.10, 1.26]). Notably, the subgroup analysis revealed that Tocilizumab had a significant effect in reducing the risk of clinical worsening compared to Sarilumab. Additionally, the analysis of mortality outcomes indicated that the administration of mAbs had the potential to decrease the overall risk of mortality over time (pooled RR: 0.90, 95 % CI [0.83, 0.97], p = 0.01). Conclusion: In summary, our meta-analysis suggests that mAbs, particularly Tocilizumab, may play a valuable role in managing COVID-19 by reducing the risk of clinical worsening, improving hospital discharge rates, and decreasing mortality.

A comprehensive, updated systematic review and meta-analysis of epidemiologic evidence on the connection between herpes zoster infection and the risk of stroke.

Stroke is a common worldwide cause of death and disability, resulting from an obstruction or reduction in blood flow to the brain. Research has demonstrated that systemic infection such as herpes zoster (HZ) / ophthalmicus herpes zoster (HZO) can potentially trigger stroke. This study includes an updated systematic review and meta-analysis of the epidemiologic data on the connection between HZ/HZO infection and the risk of stroke. A meticulous search of different database yielded 905 studies. Furthermore, an additional 14 studies from a previous meta-analysis were incorporated. Eligible studies underwent rigorous screening, resulting in 18 papers. Statistical analyses, including random/fixed effects models and subgroup analyses, were conducted to assess pooled relative risk (RR) and heterogeneity. The meta-analysis consisted of 5,505,885 participants and found a statistically significant association between HZ infection and the risk of stroke (pooled RR = 1.22, 95% confidence interval [CI] 1.12-1.34). The HZO infection showed a significantly higher overall pooled RR of 1.71 (95% CI 1.06-2.75), indicating a strong connection with the risk of stroke. Subgroup analysis revealed that the odds ratio might play a significant role in causing heterogeneity. Time since infection emerged as a crucial factor, with heightened stroke risk in the initial year post-HZ/HZO exposure, followed by a decline after the first year. Asian/Non-Asian studies demonstrated varied results in HZ/HZO patients. Meta-analysis reveals a significant HZ/HZO-stroke link. Subgroups highlight varied risks and warrant extended Asian/non-Asian patient investigation.

Regulation of immune responses to infection through interaction between stem cell-derived exosomes and toll-like receptors mediated by microRNA cargoes.

Infectious diseases are among the factors that account for a significant proportion of disease-related deaths worldwide. The primary treatment approach to combat microbial infections is the use of antibiotics. However, the widespread use of these drugs over the past two decades has led to the emergence of resistant microbial species, making the control of microbial infections a serious challenge. One of the most important solutions in the field of combating infectious diseases is the regulation of the host's defense system. Toll-like receptors (TLRs) play a crucial role in the first primary defense against pathogens by identifying harmful endogenous molecules released from dying cells and damaged tissues as well as invading microbial agents. Therefore, they play an important role in communicating and regulating innate and adaptive immunity. Of course, excessive activation of TLRs can lead to disruption of immune homeostasis and increase the risk of inflammatory reactions. Targeting TLR signaling pathways has emerged as a new therapeutic approach for infectious diseases based on host-directed therapy (HDT). In recent years, stem cell-derived exosomes have received significant attention as factors regulating the immune system. The regulation effects of exosomes on the immune system are based on the HDT strategy, which is due to their cargoes. In general, the mechanism of action of stem cell-derived exosomes in HDT is by regulating and modulating immunity, promoting tissue regeneration, and reducing host toxicity. One of their most important cargoes is microRNAs, which have been shown to play a significant role in regulating immunity through TLRs. This review investigates the therapeutic properties of stem cell-derived exosomes in combating infections through the interaction between exosomal microRNAs and Toll-like receptors.

How reliable is pre-sleeve endoscopy to characterize pathological features?

BACKGROUND: Vertical sleeve gastrectomy is a relatively new bariatric procedure with lower morbidity and mortality than other weight loss surgeries. The predictive values of preoperative esophagogastroduodenoscopy for detecting histopathological abnormalities prior to sleeve gastrectomy have not been clearly described. This study aimed to determine the negative predictive value of preoperative endoscopic biopsies for detecting Helicobacter pylori (H. pylori) infection and other pathological findings. METHODS: This cross-sectional study examined 102 patients who underwent vertical sleeve gastrectomy from January 2023 to November 2023. Preoperative histopathology of esophagogastroduodenoscopy specimens was compared to postoperative ones for H. pylori infection, gastritis, atrophy, and metaplasia. Moreover, gastroesophageal reflux disease symptoms were postoperatively followed for 6 months. RESULTS: The negative predictive value of preoperative esophagogastroduodenoscopy for detecting H. pylori infection, gastritis, metaplasia and atrophy were 95 %, 79 %, 93 %, and 98 %, respectively. In an overall view, for all pathologies, the negative predictive value was 53.4 %. Moderate gastritis and focal metaplasia were significantly underdiagnosed preoperatively (p < 0.001). H. pylori infection and focal metaplasia were significantly more prevalent in females after surgery (p < 0.001). H. pylori infection and gastritis were positively correlated with increased postoperative gastroesophageal reflux disease symptoms (p < 0.001). CONCLUSION: Preoperative endoscopy has a high negative predictive value for detecting H. pylori infection, atrophy, and metaplasia but has suboptimal values for gastritis.

Oral immunotherapy for Helicobacter pylori: Can it be trusted? A systematic review.

BACKGROUND: Helicobacter pylori (H. pylori) is a rod-shaped, gram-negative, microaerophilic bacterium that can be identified by gram staining. Its relationship with cancer is significant since it is involved in approximately 80% of gastric cancers and 5.5% of all malignant cancers. Two lines of treatment have been defined for H. pylori, but almost 40% of patients do not respond to the first line. Recent trials have investigated oral Immunotherapy as a new treatment method. The aim of this systematic review was to investigate the potential effects of oral Immunotherapy on eradication rate of H. pylori in human studies. METHODS: The systematic review was performed according to PRISMA guidelines. We searched online databases, including Scopus, PubMed, and Web of Science (ISI). Our search strategy was limited to English articles and studies on human populations that use oral immunotherapy for H. pylori. RESULTS: The total number of primary research records in different databases was 2775. After removing duplicate articles (n = 870), we excluded 1829 for reasons including non-human studies, irrelevance to our study objective, non-English language, or lack of information. Of the remaining 76 articles, only seven had sufficient information, and the rest were excluded. The studies were divided into two groups: those that used bovine antibody and those that used immunoglobulin Y to eradicate H. pylori. CONCLUSION: In the group of Immunoglobulin Y, three out of four studies suggest that using Immunoglobulin Y for the treatment of H. pylori infection is significant. However, the group using bovine antibody for the treatment of H. pylori infection has various results, as two out of three studies concluded that bovine antibody therapy is not significant.

Evaluation of autoimmune liver disease natural history in patients referred to Middle East Liver Diseases (MELD) center.

BACKGROUND: Autoimmune liver diseases (AILD) are increasing and common forms of chronic liver disease (CLD) with different clinical responses and characteristics which can result in cirrhosis. This study aimed to investigate the natural history and characteristics of AILD in an Iranian population. METHODS: Patients with AILD [Autoimmune Hepatitis (AIH), Primary Biliary Cholangitis (PBC), Primary Sclerosing Cholangitis (PSC) and Overlap Syndrome (OS)] referred to Middle East Liver Diseases (MELD) center, Tehran, Iran, between January 2002 and December 2022 were included in this retrospective cohort study. The main features of natural history (the trends of liver functional tests (LFT), Auto-Antibodies, response to treatment and cirrhotic status) along with demographic data were studied. RESULTS: Two hundred sixty-five patients (160 (60.4%) AIH, 37 (14.0%) PBC, 20 (7.5%) PSC, 48 (18.1%) overlap syndrome) with a median follow-up time of 5 years (IQR 4 to 8 years) were included. Baseline laboratory tests revealed that patients with AIH exhibit elevated transaminase levels. However, patients suffering from PBC and PSC displayed increased alkaline phosphatase levels. Conversely, in overlap syndrome patients, both transaminases and alkaline phosphatase were observed at high levels. Autoantibodies represented themselves as important diagnostic markers for the AIH and PBC but not for PSC. The complete response occurred in 112 (70%) of and 28 (58.4%) patients with AIH and overlap syndrome respectively and 21 patients 11 (6.9%) of AIH and 10 (20.8%) of overlap syndrome) were non-responders. Other patients in these two categories were considered as insufficient responders. On the other side, 32 (91.9%) and 8 (40%) of patients with PBC and PSC biochemically responded to Ursodeoxycholic Acid (UDCA). Unpredictably, cirrhosis regression was observed in some AIH and PBC patients. CONCLUSION: Appropriate medication management for AILD patients may leads to regression from cirrhosis and improvement of manifestations; while discontinuation of medication may cause relapses. However, patient suffering from PSC showed limited response to treatment.

Expression of Pivotal Long Non-coding RNAs Implicated in Gastric Cancer: A Bioinformatic and Clinical Study.

Gastric cancer (GC) is a prominent public health issue and ranks as the third most prevalent cause of cancer-related mortality on a global scale. The role of long non-coding RNAs (lncRNAs) in cancer is not yet fully understood, particularly in relation to GC development. The objective of this study was to examine the expression levels of lncRNAs in GC tissues using a bioinformatics-based ranking approach. A bioinformatics methodology was employed to prioritize lncRNAs that are hypothesized to play a role in GC tumorigenesis. Moreover, a selection was made for experimental validation of the highest-ranked lncRNAs, which include HCG18, OIP5-AS1, FGD5-AS1, and NORAD. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was employed to confirm the results obtained from bioinformatics analysis in a total of 35 GC samples and their corresponding adjacent non-tumoral samples. Receiver operating characteristic (ROC) curves and the corresponding area under the ROC curve (AUC) were utilized to evaluate the diagnostic efficacy of the lncRNAs. The bioinformatics analysis revealed that the lncRNA HCG18 is the highest-ranked lncRNA associated with GC. Furthermore, the expression levels of HCG18, OIP5-AS1, FGD5-AS1, and NORAD were found to be significantly elevated in GC samples when compared to adjacent non-tumoral samples. The calculated values for the AUC of HCG18, OIP5-AS1, FGD5-AS1, and NORAD were 0.80, 0.74, 0.73, and 0.71, respectively. The results of the study indicate that the lncRNAs HCG18, OIP5-AS1, FGD5-AS1, and NORAD may play a role in the development of GC. Additionally, the present study revealed that utilizing bioinformatic techniques can prove to be a highly effective strategy in identifying potential lncRNAs pertinent to the progression of GC.

Apatinib increases anticancer potential of doxorubicin in breast cancer cells.

BACKGROUND: In recent years, drug resistance has become a most important challenge in chemotherapy of malignancies. Here, we investigated a novel approach to enhance therapeutic potential of doxorubicin (Dox as a common chemotherapeutic drug) by co-administration of apatinib (Apa as a monoclonal antibody) in breast cancer treatment. METHODS AND RESULTS: Effects of Apa, Dox, and their combinations (Apa-Dox) were investigated on proliferation of MDA-MB-231 breast cancer cells by MTT assay. Moreover, migration and invasion of the treated and untreated control cancer cells were evaluated by scratch and transwell methods, respectively. Apoptosis percentage of the treated cancer cells was investigated by flow cytometry method. Finally, apoptosis-, metastasis-, and angiogenesis-related gene expression at mRNA and protein levels in the cancer cells were investigated by Real-Time PCR and western blotting methods, respectively. Our results indicated that treatments of cancer cells by Apa, Dox, and Apa-Dox significantly decrease proliferation, migration, and invasion of MDA-MB-231 breast cancer cells. Treatments of the breast cancer cells by Apa, Dox, and Apa-Dox significantly increase apoptosis percentage. We observed that anticancer effects of Apa, Dox, and Apa-Dox may due to modification of apoptosis-, metastasis-, and angiogenesis-related gene expression (at mRNA and protein level) in the breast cancer cells. However, anticancer potential of Apa-Dox combination was significantly more than Apa and Dox monotherapy. CONCLUSION: We demonstrated that Apa significantly increases anticancer potential of Dox in MDA-MB-231 breast cells. However, further in-vitro, in-vivo, and clinical studies are required to confirm this result.

Nano and microparticle drug delivery systems for the treatment of Brucella infections.

Nano-based drug delivery systems are increasingly used for diagnosis, prevention and treatment of several diseases, thanks to several beneficial properties, including the ability to target specific cells or organs, allowing to reduce treatment costs and side effects frequently associated with chemotherapeutic medications, thereby improving treatment compliance of patients. In the field of communicable diseases, especially those caused by intracellular bacteria, the delivery of antibiotics targeting specific cells is of critical importance to maximize their treatment efficacy. Brucella melitensis, an intracellular obligate bacterium surviving and replicating inside macrophages is hard to be eradicated, mainly because of the low ability of antibiotics to enter these phagocityc cells . Although different antibiotics regimens including gentamicin, doxycycline and rifampicin are in fact used against the Brucellosis, no efficient treatment has been attained yet, due to the intracellular life of the respective pathogen. Nano-medicines responding to environmental stimuli allow to maximize drug delivery targeting macropages, thereby boosting treatment efficacy. Several drug delivery nano-technologies, including solid lipid nanoparticles, liposomes, chitosan, niosomes, and their combinations with chitosan sodium alginate can be employed in combination of antibiotics to successfully eradicate Brucellosis infection from patients.

Knockdown of SIX4 inhibits pancreatic cancer cells via apoptosis induction.

Sine oculis homeobox 4 (SIX4), a critical transcription factor modulating organ development, potentially participates in tumorigenesis through numerous pathways. Here, we investigated siRNA-mediated knockdown effects of SIX4 on pancreatic cancer cells and underlying molecular mechanisms. The expression of SIX4 in pancreatic cancer and adjacent tissues were investigated in clinical tissue samples and bioinformatically approved by gene expression omnibus (GEO) database. Appropriate siRNA transfected into PANC1 pancreatic cancer cells in order to SIX4 knockdown. The survival, migration, invasion, colony formation, mitochondrial membrane potential, apoptosis, autophagy, and cell cycle in the cancer cells were investigated after knockdown of SIX4. In addition, expression of genes involved in apoptosis and metastasis were assessed in the transfected cancer cells in mRNA and protein levels. High-throughput analysis using GEO database confirmed the overexpression of SIX4 in pancreatic cancer tissues by six independent pancreatic cancer microarrays. Knockdown of SIX4 by specific siRNA significantly decreased survival, colony formation, and mitochondrial membrane potential of the cancer cells. Further assessments demonstrated that knockdown of SIX4 increases the apoptosis and autophagy rates in the cancer cells through modifying the expression of related genes. Moreover, a significant decrease in migration and invasion rates were observed in SIX4 suppressed group. Furthermore, frequency of the cells transfected with SIX4 siRNA increased slightly in G1 and Sub-G1 phases of cell cycle. Our study suggested that siRNA-mediated knockdown of SIX4 increases the pancreatic cancer cells death and reduces the invasion and migration of the cancer cells through different molecular pathways.

Targeted delivery of a short antimicrobial peptide (CM11) against Helicobacter pylori gastric infection using concanavalin A-coated chitosan nanoparticles.

Helicobacter pylori is the cause of most cases of stomach ulcers and also causes some digestive cancers. The emergence and spread of antibiotic-resistant strains of H. pylori is one of the most important challenges in the treatment of its infections. The present study aims to develop a concanavalin A (ConA) coated chitosan (CS) nanocarrier-based drug delivery for the targeted release of peptides to the site of H. pylori infection. Accordingly, chitosan was used as an encapsulating agent for CM11 peptide delivery by applying ionotropic gelation method. Con-A was used for coating CS nanoparticles to target H. pylori. The CS NPs and ConA-CS NPs were characterized by FTIR, dynamic light scattering (DLS), and scanning electron microscopy (SEM). The MIC of CM11-loaded ConA-CS NPs against H. pylori SS1 strain was analyzed in vitro. In order to evaluate the treatment efficiency in vivo, a gastric infection model of H. pylori SS1 strain was established in mice and histopathological studies and IL-1ß cytokine assay were performed. Based on the results, the size frequency for CS NPs and ConA-CS NPs was about 200 and 350 nm, respectively. The prepared CM11-loaded ConA-CS NPs exhibited antibacterial activity against H. pylori SS1 strain with a concentration of 32 µg/ml. The highest healing process was observed in synthesized CM11-loaded ConA-CS NPs treatments and a significant decrease in IL-1ß was observed. Our findings highlight the potential of chitosan nanoparticles as a drug delivery vehicle in the treatment of gastric infection model of H. pylori SS1 strain.

The CD8+ T cell exhaustion mechanisms in chronic hepatitis B infection and immunotherapeutic strategies: a systematic review.

INTRODUCTION: The hepatitis B virus (HBV) continues to be a leading cause of morbidity and mortality worldwide. In developing countries, HBV is the most common etiology of those liver diseases such as chronic hepatitis B (CHB), acute hepatitis B (AHB), acute-on-chronic liver failure (ACLF), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). CD8+ T cell exhaustion is a condition of T cell malfunction and reduction that plays a crucial role in the progression of HBV infection. AREAS COVERED: This systematic review attempts to evaluate the main inhibitory mechanisms involved in CD8+ T cell exhaustion, in different clinical phases of HBV infection and relation to disease progression. A systematic search in PubMed, Web of Science, and Scopus was performed to identify articles published in English till October 2022. EXPERT OPINION: According to the numerous conducted studies, we conclude that CD8+ T cell exhaustion commonly occurs in the tumoral and chronic suppressive environment and CHB and HCC patients; furthermore, this phenomenon is less seen in AHB and ACLF patients. The emergence of surficial inhibitory receptors (IRs) on CD8+ T cells is the leading cause of exhaustion, and programmed cell death protein-1 (PD-1) has much importance among the others.

Emerging Role of Tumor-Educated Platelets as a New Liquid Biopsy Tool for Colorectal Cancer.

Colorectal cancer (CRC) is a major cause of cancer-associated death universally. Currently, the diagnosis, prognosis, and treatment monitoring of CRC mostly depends on endoscopy integrated with tissue biopsy. Recently, liquid biopsy has gained more and more attention in the area of molecular detection and monitoring of tumors due to ease of sampling, and its safe, non-invasive, and dynamic nature. Platelets, despite their role in hemostasis and thrombosis, are known to have an active, bifacial relationship with cancers. Platelets are the second most common type of cell in the blood and are one of the wealthy liquid biopsy biosources. These cells have the potential to absorb nucleic acids and proteins and modify their transcriptome with regard to external signals, which are termed tumor-educated platelets (TEPs). Liquid biopsies depend on TEPs' biomarkers which can be used to screen and also detect cancer in terms of prognosis, personalized treatment, monitoring, and prediction of recurrence. The value of TEPs as an origin of tumor biomarkers is relatively new, but platelets are commonly isolated using formidable and rapid techniques in clinical practice. Numerous preclinical researches have emphasized the potential of platelets as a new liquid biopsy biosource for detecting several types of tumors. This review discusses the potential use of platelets as a liquid biopsy for CRC.

The Trend of IgG and IgM Antibodies During 6-Month Period After the Disease Episode in COVID-19 Patients.

SARS-CoV-2 is a newly emerged coronavirus that has been widely transmitted since late 2019. It has caused a pandemic and infected roughly 450 million people globally.Hitherto, there is no approved anti-COVID-19 treatment, and vaccination is the only experienced preventive strategy. It mainly promotes the immune system, which is vital as a barrier against COVID-19. Humoral immunity (antibody-mediated immunity), among the various functions of the immune system against the coronavirus, plays an outstanding role in preventing infection. Consequently, we intended to assess IgG and IgM antibodies, 3 and 6 months after infection, to trend their titer and see how long COVID-19 antibodies remained in the human body. According to the research-designed criteria, only 98 patients out of 4500 suspected cases of SARS-CoV-2 infection remained for analysis. Blood samples were taken in three time periods (Day Zero (T 0), 3 and 6 months post-infection) and examined for COVID-19's IgG and IgM antibodies titration using the ELISA platform. Though both IgG and IgM were still detectable for some subjects at the end of the period, the decline in their levels (from 14.45 ± 5.88 to 2.52 ± 2.33 for IgG [85% decline of antibody titer] and 8.3 ± 0.99 to 0.37 ± 0.14 for IgM [95.5% decline of antibody titer]) was statistically significant (P value 0.0001). There was no correlation between gender and IgG and IgM levels. Although the levels of both antibodies were overall higher in the senior group (≥ 60 years old), statistical analysis showed a significantly higher level just for IgM in this group (P value: 0.005). Following the results, although anti-SARS-CoV-2 IgM and IgG antibodies can persist in the blood for 6 months post-infection, their levels steeply declined over time. Therefore, relying on humoral immunity as a trustworthy barrier against SARS-CoV-2 infection calls for more extensive research. Supplementary Information: The online version contains supplementary material available at 10.1007/s40995-022-01382-7.

Coronavirus Disease 2019 (COVID-19) Infection-Related Stigma, Depression, Anxiety, and Stress in Iranian Healthcare Workers.

Background: Psychological conditions aggravate during outbreaks. Here, we have discussed the existing COVID-19 depression, anxiety, and stress and the resulting stigma and its different aspects in Iranian health care workers and their 1st-degree relatives. Methods: In this cross-sectional study, information of our study groups (237 participants including health care workers and their nuclear family members) was collected via two online stigma and depression, anxiety, and stress scale (DASS) questionnaires. Results: The DASS questionnaire's mean depression, anxiety, and stress scores were 13.59 ± 5.76, 11.07 ± 4.38, and 15.05 ± 5.86, respectively, in our study population. Marriage status was effective on depression and stress scores. Married participants were having less depression (P = 0.008) but more stressful (P = 0.029) than single ones. Education was found to be effective on anxiety and stress scores. Those with an associate, master, Ph.D., and higher college degrees were significantly less anxious and stressed than those with a diploma or bachelor's degrees (P = 0.032 and 0.016, respectively, for anxiety and stress). Participants with a history of psychiatric conditions showed significantly higher depression, anxiety, and stress rates than those without a past psychiatric condition (P = 0.001). Healthcare workers and their nuclear family members suffer from severe stigma (mean stigma scores were 33.57 and 33.17, respectively). Conclusions: Healthcare workers and their nuclear family members in Iran suffer from severe COVID-19 related stigma. We also showed that depression, anxiety, and stress are common among Iranian Healthcare workers and their nuclear family members during this pandemic. This study showed that people with preexisting psychiatric conditions need extra mental care during the pandemic.

A New Combination: Anti Glypican-3 scFv and Diphtheria Toxin with the Best Flexible Linker.

Along with all cancer treatments, including chemotherapy, radiotherapy, and surgery, targeting therapy is a new treatment manner. Immunotoxins are new recombinant structures that kill cancer cells by targeting specific antigens. Immunotoxins are composed of two parts: toxin moiety, which disrupts protein synthesis process, and antigen binding moiety that bind to antigens on the surface of cancer cells. Glypican 3 (GPC3) is an oncofetal antigen on the surface of Hepatocellular carcinoma (HCC) cells. In this study, truncated Diphtheria toxin (DT389) was fused to humanized scFv YP7 by one, two and three repeats of GGGGS linkers (DT389-(GGGGS)1-3YP7). In-silico and experimental investigation were performed to find out how many repeats of linker between toxin and scFv moieties are sufficient. Results of in-silico investigations revealed that the difference in the number of linkers does not have a significant effect on the main structures of the immunotoxin; however, the three-dimensional structure of two repeats of linker had a more appropriate structure compared to others with one and three linker replications. In addition, with enhancing the number of linkers, the probability of protein solubility has increased. Generally, the bioinformatics results of DT389-(GGGGS)2-YP7 structure showed that expression and folding is suitable; and YP7 scFv has appropriate orientation to bind GPC3. The experimental investigations indicated that the fusion protein was expressed as near to 50% soluble. Due to the high binding affinity of YP7 scFv and the proven potency of diphtheria in inhibiting protein synthesis, the proposed DT389-(GGGGS)2-YP7 immunotoxin is expected to function well in inhibiting HCC.

Synthesis and characterization of phase shift dextran stabilized nanodroplets for ultrasound-induced cancer therapy: A novel nanobiotechnology approach.

The nanobiotechnology, one heck of a biotechnology approach, is considered as a focal point in drug delivery systems. Although, plenty of novel approaches are reported in this area, it tackles with strict challenged which confine its broad application. Therefore, there is a need to dig deep into it along with all details. Here, a novel nanobiotechnology approach is described in detail for synthesis and characterization of phase shift dextran stabilized nanodroplets for ultrasound-induced cancer therapy. The aim of this work was to study the effect of parameters including homogenization speed and formulation of dextran and surfactant concentrations on particle size, entrapment efficiency and drug release kinetics of dextran stabilized perfluorohexane nanodroplets containing doxorubicin (Dox) drug. The obtained results showed that the particle size and encapsulation efficiency significantly increased by increasing polymer concentration. In addition, by increasing the homogenization speed, the particle size was increased while entrapment efficiency was decreased. On the other hand, by increasing the surfactant concentration, the particle size and entrapment efficiency reached to optimum values of 47.2 nm and 80.2%, respectively. In vitro release profile of doxorubicin was an apparently biphasic release process and 7-13% of drug was released after 24 h incubation in PBS with pH of 5.5, depending on the nanodroplets (ND) composition. Ultrasound exposure for 10 min resulted in triggered release of 82.95% of Dox from optimal formulation of sample C3 (0.1%w/v dextran, homogenization speed of 24000 rpm and Dox content of 500 µg).

Outlook of therapeutic and diagnostic competency of nanobodies against SARS-CoV-2: A systematic review.

PURPOSE: The newly emerged coronavirus (SARS-CoV-2) continues to infect humans, and no completely efficient treatment has yet been found. Antibody therapy is one way to control infection caused by COVID-19, but the use of classical antibodies has many disadvantages. Heavy chain antibodies (HCAbs) are single-domain antibodies derived from the Camelidae family. The variable part of these antibodies (Nanobodies or VHH) has interesting properties such as small size, identify criptic epitopes, stability in harsh conditions, good tissue permeability and cost-effective production causing nanobodies have become a good candidate in the treatment and diagnosis of viral infections. METHODS: Totally 157 records (up to November 10, 2021), were recognized to be reviewed in this study. 62 studies were removed after first step screening due to their deviation from inclusion criteria. The remaining 95 studies were reviewed in details. After removing articles that were not in the study area, 45 remaining studies met the inclusion criteria and were qualified to be included in the systematic review. RESULTS: In this systematic review, the application of nanobodies in the treatment and detection of COVID-19 infection was reviewed. The results of this study showed that extensive and sufficient studies have been performed in the field of production of nanobodies against SARS-CoV-2 virus and the obtained nanobodies have a great potential for use in patients infected with SARS-CoV-2 virus. CONCLUSION: According to the obtained results, it was found that nanobodies can be used effectively in the treatment and diagnosis of SARS-CoV-2 virus.

Predictors of survival rate in patients with pancreatic cancer: A multi-center analytical study in Iran.

BACKGROUND: Pancreatic cancer (PC) is among the deadliest cancers of the gastrointestinal tract worldwide and a growing global health concern. AIM: This study was aimed to evaluate the survival rate and prognostic factors of survival in patients with PC. METHODS: In this retrospective cohort study, the records of 556 patients with PC registered in the hospital cancer registration system from September 2007 to September 2020 were evaluated. In this regard, demographic data, tumor characteristics, received treatments, and patients' final status were analyzed. Kaplan-Meier and Cox's regression were used for univariate and multivariate analyses, respectively. RESULTS: The 5-year survival rate was found to be 4.3%. The median survival time was 12.4 ± 6.6 months. Univariate analysis showed that age, BMI (kg/m2 ), blood transfusions, differentiation, tumor stage, tumor size, number of involved lymph nodes, lymph node ratio (LNR), and type of treatment received were significantly associated with patient survival (p < .05). Multivariate Cox regression indicated that the age ≥60 years [Hazard Ratio (HR) = 1.25, 95% confidence interval (CI) = 1.03-1.49], BMI <18 (kg/m2 ; HR = 1.56, 95% CI = 1.13-2.14), poor differentiation (HR = 2.12, 95% CI = 1.75-2.49), tumor size >2.5 cm (HR = 4.61, 95% CI = 3.30-6.78), metastasis presence (HR = 1.97, 95% CI = 1.49-2.60), more than two involved lymph nodes (HR = 1.52, 95% CI = 1.31-1.77), LNR <0.2 (HR = 0.56, 95% CI = 0.36-0.77), and adjuvant therapy with surgery and chemotherapy (HR = 0.44, 95% CI = 0.28-0.61) are the most important prognostic factors of survival in patients with PC (p < .05). CONCLUSIONS: This study showed that the survival rate of patients with pancreatic cancer varies based on the characteristics of the tumor and the type of treatment received.