The power of Punica granatum: A natural remedy for oxidative stress and inflammation; a narrative review.

ETHNOPHARMACOLOGICAL RELEVANCE: Pomegranate 'Punica granatum' offers multiple health benefits, including managing hypertension, dyslipidemia, hyperglycemia, insulin resistance, and enhancing wound healing and infection resistance, thanks to its potent antioxidant and anti-inflammatory properties. It has been symbolized by life, health, femininity, fecundity, and spirituality. AIM OF THE STUDY: Although laboratory and animal studies have been conducted on the healing effects of pomegranate, there needs to be a comprehensive review on its anti-oxidative and anti-inflammatory effects in chronic disorders. We aim to provide a comprehensive review of these effects based on in-vitro, in-vivo, and clinical studies conducted in managing various disorders. MATERIALS AND METHODS: A comprehensive search of in-vitro, in-vivo, and clinical findings of pomegranate and its derivatives focusing on the highly qualified original studies and systematic reviews are carried out in valid international web databases, including Web of Science, PubMed, Scopus, and Cochrane Library. RESULTS: Relevant studies have demonstrated that pomegranate and its derivatives can modulate the expression and activity of several genes, enzymes, and receptors through influencing oxidative stress and inflammation pathways. Different parts of pomegranate; roots, bark, blossoms, fruits, and leaves contain various bioactive compounds, such as polyphenols, flavonoids, anthocyanins, and ellagitannins, that have preventive and therapeutic effects against many disorders such as cardiovascular diseases, diabetes, neurological diseases, and cancers without any serious adverse effects. CONCLUSIONS: Most recent scientific evidence indicates that all parts of the pomegranate can be helpful in treating a wide range of chronic disorders due to its anti-oxidative and anti-inflammatory activities. Since the safety of pomegranate fruit, juice, and extracts is established, further investigations can be designed by targeting its active antioxidant and anti-inflammatory constituents to discover new drugs.

Combined cross-linking of Rhizomucor miehei lipase and Candida antarctica lipase B for the effective enrichment of omega-3 fatty acids in fish oil.

The incorporation of a non-specific lipase and a sn-1,3 specific one in a single immobilized system can be a promising approach for the exploitation of both lipases. A one-step immobilization platform mediated by an isocyanide-based multi-component reaction was applied to create co-cross-linked enzymes (co-CLEs) of lipases from Rhizomucor miehei (sn-1,3 specific) and Candida antarctica (non-specific). Glutaraldehyde was found to be effective cross-linker by producing specific activity of 16.9 U/mg and immobilization yield of 99 %. High activity recovery of up to 404 % was obtained for immobilized derivatives. Leaking experiment showed covalent nature of the cross-linking processes. BSA had considerable effect on the immobilization process, providing 87-100 % immobilization yields and up to 10 times improvement in the specific activity of the immobilized derivatives. Scanning electron microscopy images showed flower-like and rod-like structures for the CLEs prepared by glutaraldehyde and undecanedicarboxylic acid, respectively. The prepared co-CLEs were examined in non-selective enrichment of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil, showing capability of releasing up to 100 % of both omega-3 fatty acids within 8 h of the reaction. The reusability of co-CLEs in five successive cycles presented retaining 63-72 % of their initial activities after the fifth reuse cycle in the hydrolysis reaction.

Unraveling the link between insulin resistance and Non-alcoholic fatty liver disease (or metabolic dysfunction-associated steatotic liver disease): A Narrative Review.

Objective: Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming a significant global health concern, representing the leading cause of chronic liver disease and posing a substantial public health challenge. NAFLD is associated with higher insulin resistance (IR) levels, a key pathophysiological mechanism contributing to its development and progression. To counter this growing trend, it is crucial to raise awareness about NAFLD and promote healthy lifestyles to mitigate the impact of this disease. Methods: Relevant studies regarding IR and NAFLD published until May 30, 2023, were extracted from Google PubMed, Scopus, and Web Of Science web databases. The following keywords were used: IR, diabetes mellitus, Non-alcoholic fatty liver disease, and metabolic syndrome. Results: IR leads to an accumulation of fatty acids within liver cells, resulting from increased glycolysis and decreased apolipoprotein B-100. Furthermore, the manifestations of NAFLD extend beyond liver-related morbidity and mortality, affecting multiple organs and giving rise to various non-communicable disorders such as diabetes mellitus, metabolic syndrome, polycystic ovary syndrome, obstructive sleep apnea, and cardiovascular disease. Although lifestyle modification remains the primary treatment approach for NAFLD, alternative therapies, including pharmacological, herbal, and surgical interventions, may be considered. By implementing early and simple measures, cirrhosis, end-stage liver disease, and hepatocellular carcinoma can be prevented. Conclusions: There is a clear association between NAFLD and elevated levels of IR. Several metabolic conditions, such as obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome, are closely interrelated with NAFLD and IR. Raising awareness about NAFLD and promoting a healthy lifestyle are crucial steps to reverse the impact of this disease.

A Novel Electrokinetic-Based Technique for the Isolation of Circulating Tumor Cells.

The separation of rare cells from complex biofluids has attracted attention in biological research and clinical applications, especially for cancer detection and treatment. In particular, various technologies and methods have been developed for the isolation of circulating tumor cells (CTCs) in the blood. Among them, the induced-charge electrokinetic (ICEK) flow method has shown its high efficacy for cell manipulation where micro-vortices (MVs), generated as a result of induced charges on a polarizable surface, can effectively manipulate particles and cells in complex fluids. While the majority of MVs have been induced by AC electric fields, these vortices have also been observed under a DC electric field generated around a polarizable hurdle. In the present numerical work, the capability of MVs for the manipulation of CTCs and their entrapment in the DC electric field is investigated. First, the numerical results are verified against the available data in the literature. Then, various hurdle geometries are employed to find the most effective geometry for MV-based particle entrapment. The effects of electric field strength (EFS), wall zeta potential magnitude, and the particles' diameter on the trapping efficacy are further investigated. The results demonstrated that the MVs generated around only the rectangular hurdle are capable of trapping particles as large as the size of CTCs. An EFS of about 75 V/cm was shown to be effective for the entrapment of above 90% of CTCs in the MVs. In addition, an EFS of 85 V/cm demonstrated a capability for isolating particles larger than 8 µm from a suspension of particles/cells 1-25 µm in diameter, useful for the enrichment of cancer cells and potentially for the real-time and non-invasive monitoring of drug effectiveness on circulating cancer cells in blood circulation.

Comparison of different transient gene expression systems for the production of a new humanized anti-HER2 monoclonal antibody (Hersintuzumab).

BACKGROUND: Producing therapeutic proteins can be done quickly and on a large scale through Transient Gene Expression (TGE). Chinese hamster ovary (CHO) cell lines are commonly used to achieve this. Although there are few comparative studies, TGE has been observed in suspension-adapted CHO cells. OBJECTIVES: We tested TGE's effectiveness in DG-44, CHO-S, and ExpiCHO-S cell lines with four transfection reagents. METHODS: A design of experiments (DoE) was followed to optimize transfection using a recombinant monoclonal antibody (mAb) construct. To evaluate the efficacy, flow cytometry and ELISA were used. Feeding strategies and temperature shifts were implemented to enhance transfection effectiveness. The quality of the mAb was assessed through ELISA, SDS-PAGE, and proliferation inhibition assays. RESULTS: We adapted all cell lines to grow in suspension using a serum-free medium. Our findings from flow cytometry and ELISA tests indicate that PEI and Pmax reagents had a higher rate of transfection and mAb production than the ExpiCHO commercial transfection reagent. While DG-44 cells had better transfection efficiency than CHO-S and ExpiCHO-S, there was no significant difference between CHO-S and ExpiCHO-S. Our TGE system was more productive at 32 °C than at 37 °C. In the optimized TGE of Pmax-based transfection in DG-44 at 37 and 32 °C, the production level of mAb was more than half of the amount of the commercial ExpiCHO-S expression system. Still, the number of transfected cells was three times higher, making it more efficient. The purified mAb from all transfected cell lines had similar structural and functional properties under different conditions. CONCLUSION: Our research shows that using Pmax and DG-44 cells in the TGE system is a cost-effective and efficient way to produce humanized monoclonal antibodies. We discovered that this method outperforms the ExpiCHO-S kit.

Peptiligase, an enzyme for efficient chemo-enzymatic synthesis of aviptadil.

Increasing attention to peptides as prospective therapeutics has created a renaissance in searching for new alternatives to the current peptide synthetic approaches as well as their modification. In this context, it is necessary to develop different approaches for peptide ligation. Using enzymes as a novel strategy and powerful tool for the peptide and protein ligation has recently received a lot of attention. We here designed a fully convergent chemo-enzymatic peptide synthesis (CEPS) process for the synthesis of aviptadil a 28-mer therapeutic peptide with potential therapeutic effects in various medical contexts specially in the treatment of acute respiratory distress syndrome (ARDS) by coupling two peptide segments with four different peptiligase variants in aqueous environments. Our study reveals that peptiligase variants are capable of ligation reaction in 15 min. The overall time of ligation is shorter than those peptides with similar lengths and hinderance to aviptadil which reported for conventional synthesis by full solid-phase peptide synthesis. Yields ranged from 54 % to 76 %.

Biocatalytic synthesis of oxadiazole thioethers and evaluation of their antitumor activity.

A multicomponent enzyme-catalyzed process is suggested for the synthesis of a novel series of 1,3,4-oxadiazole thioether derivatives with yields ranging from 65 to 94%. Novozym 435, the immobilized form of Candida antarctica lipase B (CALB), was found to efficiently catalyze the reaction. The products were evaluated for antitumor activities against two cancer cell lines, HT-29 (human colorectal cancer cell) and HepG2 (human liver cancer cell), by MTT assays. Among them, two compounds exhibited higher antitumor activities, for both cell lines, compared to doxorubicin. In silico molecular docking and computational ADME analysis were performed to propose a mode of action for the anti-cancer activities and to predict drug-likeness, respectively.

The current regenerative medicine approaches of craniofacial diseases: A narrative review.

Craniofacial deformities (CFDs) develop following oncological resection, trauma, or congenital disorders. Trauma is one of the top five causes of death globally, with rates varying from country to country. They result in a non-healing composite tissue wound as they degenerate in soft or hard tissues. Approximately one-third of oral diseases are caused by gum disease. Due to the complexity of anatomical structures in the region and the variety of tissue-specific requirements, CFD treatments present many challenges. Many treatment methods for CFDs are available today, such as drugs, regenerative medicine (RM), surgery, and tissue engineering. Functional restoration of a tissue or an organ after trauma or other chronic diseases is the focus of this emerging field of science. The materials and methodologies used in craniofacial reconstruction have significantly improved in the last few years. A facial fracture requires bone preservation as much as possible, so tiny fragments are removed initially. It is possible to replace bone marrow stem cells with oral stem cells for CFDs due to their excellent potential for bone formation. This review article discusses regenerative approaches for different types of craniofacial diseases.

A Novel Fc-Engineered Anti-HER2 Bispecific Antibody With Enhanced Antitumor Activity.

Human epidermal growth factor receptor 2 (HER2) overexpression has been demonstrated in a variety of cancers. Targeted therapy with anti-HER2 monoclonal antibodies (mAbs) has been approved as a therapeutic modality. Despite the efficacy of mAbs in tumor treatment, many patients do not benefit from this therapeutic platform. Fragment crystallizable (Fc) engineering is a common approach to improve the efficacy of therapeutic mAbs. Five Fc-engineered mAbs have so far been approved by FDA. We have recently developed an anti-HER2 bispecific mAb, BiHT, constructed from variable domains of trastuzumab, and our novel humanized anti-HER2 mAb, hersintuzumab. BiHT displayed promising antitumor activity as potently as the combination of the parental mAbs. Here, we aimed to modify the Fc of BiHT to improve its therapeutic efficacy. The Fc-engineered BiHT (MBiHT) bound to recombinant HER2 and its subdomains with an affinity similar to BiHT. It also recognized native HER2 on different cell lines, inhibited their proliferation, downregulated HER2 expression, and suppressed downstream signaling pathways similar to BiHT. Compared with BiHT, MBiHT displayed enhanced antibody-dependent cellular cytotoxicity activity against various tumor cell lines. It also inhibited the growth of ovarian xenograft tumors in nude mice more potently than BiHT. Our findings suggest that MBiHT could be a potent therapeutic candidate for the treatment of HER2-overexpressing cancer types.

Adherence to practice guidelines for the management of febrile neutropenia in patients undergoing hematopoietic stem cell transplantation: An observational study in a referral center in Iran.

INTRODUCTION: Patients undergoing hematopoietic stem cell transplantation (HSCT) are suspected to develop febrile neutropenia (FN) and severe infections. Therefore, appropriate prescription of antibiotics in these patients is crucial to reduce the rates of morbidity, mortality, and antimicrobial resistance. The present study aimed to evaluate the physicians' prescription and adherence to the FN clinical guidelines among patients undergoing HSCT. METHODS: This prospective observational single-center study was conducted during a 15-month period in a tertiary referral hospital in Iran. The patients with at least one episode of FN following HSCT were included in the current study. The physicians' adherence to the Infectious Diseases Society of America (IDSA) and National Comprehensive Cancer Network (NCCN) clinical guidelines for the management of FN was evaluated using prescription data and medical record reviews. RESULTS: Two hundred and fifteen patients with 297 FN episodes were evaluated. The timing of antibiotics and the selection of the initial regimen were considered guideline-based therapy. However, antibiotic dosing and initial regimen modification were not followed in terms of the guideline recommendations in 58.1% of the patients. In particular, vancomycin was inappropriately given in 83.1% of patients. The overall adherence of physicians to the guidelines was 35.8%. CONCLUSION: Non-adherence to clinical guidelines is high particularly in initial regimen modification and administration of vancomycin, which affects hospital stay and patient's outcome. Implementation of guideline-review sessions to raise the awareness of the physicians and to improve the rational use of antimicrobial agents may be crucial.

The Benefits of Promoting Junior Trainees in Vascular Surgery.

Introduction United Kingdom surgical training consists of a two-year core surgical training (CST) followed by a six-year higher speciality training (ST). There is a significant step up in responsibility and operative skills when transitioning from core to higher training. One-way trainees can bridge this gap is to "act up" to registrar level "CST-R." The CST "steps up" to the role of ST typically in the latter part of their core training and gains exposure at being the "reg of the week," primary assistant in theatre, managing MDTs, and taking speciality referrals. This can be an excellent training opportunity. This study aims to demonstrate a quantitative improvement in trainee operation as a result of stepping up. Methods This study compares the operative experience of one vascular surgery-themed trainee during six months as a CST and six months acting up as a CST-R. The trainee's eLogbook was searched for all operations between August 3, 2022, and January 31, 2023, and between February 1, 2023, and August 1, 2023. The number of cases performed and the role played in each were analyzed. The number of low complexity cases conducted in each block was used as a baseline to ensure the progression seen was because of increasingly complex ST operating rather than the increase in CST level operating expected throughout CST. An abscess incision and drainage were used as the reference low-complexity case. Results The number of cases the trainee performed independently increased from 13% to 25%, while the number where they were simply assisting decreased from 43% to 35%. The number of cases where the trainer remained scrubbed decreased nonsignificantly from 43% to 39%. The number of low-complexity cases performed remained unchanged for each six-month block. Conclusion As a CST-R, the trainee played a more prominent operative role in a greater number of cases. The CST-R does require a supportive department and consultant body. It also enables other STs to gain more surgical exposure because of their reduced frequency of being the "reg of the week." If a trainee can remain in a post for two six-month blocks, then there is much to be gained from a formalised acting-up program, and consideration should be given to formally incorporating this into core surgical programs.

Diarylation of thiazolopyrimidines by laccase and their in vitro evaluation as antitumor agents.

A mild and efficient method was developed for the synthesis of new derivatives of thiazolo[3,2-a] pyrimidin-3(2H)-ones from available starting materials based on the oxidation of catechols to ortho-quinone by Myceliophthora thermophila laccase (Novozym 51,003) and 1,4-addition of active methylene carbon to these in situ generated intermediates in moderate to good yields (35-93%). The structure of the products was confirmed through 1H NMR, 13C NMR, HMBC, HSQC, DEPT-135, and mass spectroscopy techniques. These novel compounds were evaluated as active antitumor agents against human colorectal adenocarcinoma and liver adenocarcinoma cell lines. All compounds displayed potent inhibition activities against the HT-29 cell line with IC50 values of 9.8-35.9 µM, superior to the positive control doxorubicin, and most showed potent anticancer activities against the HepG2 cell line.

A multi-component approach for co-immobilization of lipases on silica-coated magnetic nanoparticles: improving biodiesel production from waste cooking oil.

The capability of multi-component reactions in rapid immobilization of enzymes was considered for co-immobilization of Thermomyces lanuginous lipase (TLL) and Candida antarctica lipase B (CALB) [TLL: CALB]; Rhizomucor miehei lipase (RML) and CALB [RML: CALB] on amine-functionalized silica-coated magnetic nanoparticles (Fe3O4@SiO2-NH2). Immobilization of different ratios of lipases was performed within 3 h under mild conditions; producing specific activity ranging from 29 to 35 U/mg for TLL:CALB and 21-34 U/mg for RML:CALB. The co-immobilized derivatives showed improved co-solvent and thermal stability compared to the corresponding free enzymes. All the derivatives were also used to catalyze the transesterification of waste cooking oil with methanol to produce biodiesel (fatty acid methyl esters). Response surface method (RSM) and a central composite rotatable design (CCRD) were used to study the effects of different factors on the FAME yield. Fe3O4@SiO2-NH2-RML-CALB and Fe3O4@SiO2-NH2-TLL-CALB had maximum FAME yields of 99-80%, respectively.

A multi-component reaction for covalent immobilization of lipases on amine-functionalized magnetic nanoparticles: production of biodiesel from waste cooking oil.

A new approach was used for the immobilization of Thermomyces lanuginosus lipase (TLL), Candida antarctica lipase B (CALB), and Rhizomucor miehei lipase (RML) on amine-functionalized magnetic nanoparticles (Fe3O4@SiO2-NH2) via a multi-component reaction route (using cyclohexyl isocyanide). The used method offered a single-step and very fast process for covalent attachment of the lipases under extremely mild reaction conditions (25 °C, water, and pH 7.0). Rapid and simple immobilization of 20 mg of RML, TLL, and CALB on 1 g of the support produced 100%, 98.5%, and 99.2% immobilization yields, respectively, after 2 h of incubation. The immobilized derivatives were then used for biodiesel production from waste cooking oil. Response surface methodology (RSM) in combination with central composite rotatable design (CCRD) was employed to evaluate and optimize the biodiesel production. The effect of some parameters such as catalyst amount, reaction temperature, methanol concentration, water content for TLL or water-adsorbent for RML and CALB, and ratio of t-butanol (wt%) were investigated on the fatty acid methyl esters (FAME) yield.

Incidence of and factors associated with metabolic syndrome, south-east Islamic Republic of Iran.

BACKGROUND: Metabolic syndrome is an important cause of cardiovascular disease. Mortality from cardiovascular disease is 12.82 deaths/100 000 population in Zahedan, south-east Islamic Republic of Iran. AIMS: This study aimed to determine the incidence of metabolic syndrome and its predicting factors in Zahedan city. METHODS: All participants without metabolic syndrome in a 2009 study in Zahedan, available in 2017, were included in this study. Metabolic syndrome was diagnosed based on the criteria of several organizations. Anthropometric indices and blood pressure were measured and blood tests were done. Age-standardized incidence of metabolic syndrome was calculated and its predictors were evaluated in a logistic regression analysis. RESULTS: Mean age (standard deviation) of the participants was 45.46 (12.63) years in 2017. The incidence of metabolic syndrome varied from 17.21% to 27.18% depending on the criteria used and it was higher in women. High age-standardized incidence was associated with large waist circumference (55.81%) and high blood pressure (25.32%). The highest adjusted odds ratios (OR) for metabolic syndrome were for high triglycerides (OR = 23.75; 95% confidence interval (CI): 9.92-56.84%), large waist circumference (OR = 22.42; 95% CI: 9.03-55.70%), high blood pressure (OR = 16.91; 95% CI: 8.54-33.50%) and high fasting blood sugar (OR = 13.22; 95% CI: 6.74-25.94%). Waterpipe smoking, sex, low-density lipoprotein and wrist circumference were also associated with metabolic syndrome. CONCLUSIONS: The incidence of metabolic syndrome has increased in Zahedan. Effective, interventions, including to promote healthy diet, physical activity and avoidance of waterpipe smoking, are needed to control this condition.

Novel Silver-Functionalized Poly(ε-Caprolactone)/Biphasic Calcium Phosphate Scaffolds Designed to Counteract Post-Surgical Infections in Orthopedic Applications.

In this study, we designed and developed novel poly(ε-caprolactone) (PCL)-based biomaterials, for use as bone scaffolds, through modification with both biphasic calcium phosphate (BCP), to impart bioactive/bioresorbable properties, and with silver nitrate, to provide antibacterial protection against Staphylococcus aureus, a microorganism involved in prosthetic joint infections (PJIs). Field emission scanning electron microscopy (FESEM) showed that the samples were characterized by square-shaped macropores, and energy dispersive X-ray spectroscopy analysis confirmed the presence of PCL and BCP phases, while inductively coupled plasma-mass spectrometry (ICP-MS) established the release of Ag+ in the medium (~0.15-0.8 wt% of initial Ag content). Adhesion assays revealed a significant (p < 0.0001) reduction in both adherent and planktonic staphylococci on the Ag-functionalized biomaterials, and the presence of an inhibition halo confirmed Ag release from enriched samples. To assess the potential outcome in promoting bone integration, preliminary tests on sarcoma osteogenic-2 (Saos-2) cells indicated PCL and BCP/PCL biocompatibility, but a reduction in viability was observed for Ag-added biomaterials. Due to their combined biodegrading and antimicrobial properties, the silver-enriched BCP/PCL-based scaffolds showed good potential for engineering of bone tissue and for reducing PJIs as a microbial anti-adhesive tool used in the delivery of targeted antimicrobial molecules, even if the amount of silver needs to be tuned to improve osteointegration.

The dietary effect of fucoidan extracted from brown seaweed, Cystoseira trinodis (C. Agardh) on growth and disease resistance to WSSV in shrimp Litopenaeus vannamei.

The polysaccharide-fucoidan plays a fundamental role in shrimp aquaculture by being used as a natural immunostimulant and dietary supplementation. In this study, Cystoseira trinodis fucoidan (FCT) was extracted, its structure was determined using FT-IR analysis, and its effect of fucoidan on growth performance and WSSV resistance in Litopenaeus vannamei was evaluated. Four experimental diets, including the control (without FCT), 0.1, 0.2, and 0.4% FCT, were formulated and fed to shrimps for 60 days. Next, they were exposed to WSSV, and their mortality rate was noted daily up to 20 days. The results of the growth experiment demonstrated a significant increase in the final weight, WG, and SGR, and a lower FCR in treatments than in control. During the challenge trial, 100% mortality was recorded in control within ten days. However, FCT-treated shrimps indicated a mortality increase from 43.33 to 75.00% during 20 days of infection. The immunological and biochemical parameters and the expression of immune-related genes in individuals fed the FCT-incorporated diet considerably (p < 0.01) improved over control before the challenge (0 days) and after the challenge on days 5, 10, 15, and 20. It was concluded that L. vannamei fed on diets supplemented with all concentrations of FCT (especially 0.4%) had improved the growth, immunological and biochemical parameters, and the expression of immune-related genes, as well as enhancing the resistance against WSSV.

Efficacy and Safety of COVID-19 Vaccines: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

The current study systematically reviewed, summarized and meta-analyzed the clinical features of the vaccines in clinical trials to provide a better estimate of their efficacy, side effects and immunogenicity. All relevant publications were systematically searched and collected from major databases up to 12 March 2021. A total of 25 RCTs (123 datasets), 58,889 cases that received the COVID-19 vaccine and 46,638 controls who received placebo were included in the meta-analysis. In total, mRNA-based and adenovirus-vectored COVID-19 vaccines had 94.6% (95% CI 0.936-0.954) and 80.2% (95% CI 0.56-0.93) efficacy in phase II/III RCTs, respectively. Efficacy of the adenovirus-vectored vaccine after the first (97.6%; 95% CI 0.939-0.997) and second (98.2%; 95% CI 0.980-0.984) doses was the highest against receptor-binding domain (RBD) antigen after 3 weeks of injections. The mRNA-based vaccines had the highest level of side effects reported except for diarrhea and arthralgia. Aluminum-adjuvanted vaccines had the lowest systemic and local side effects between vaccines' adjuvant or without adjuvant, except for injection site redness. The adenovirus-vectored and mRNA-based vaccines for COVID-19 showed the highest efficacy after first and second doses, respectively. The mRNA-based vaccines had higher side effects. Remarkably few experienced extreme adverse effects and all stimulated robust immune responses.

Emerging technologies and commercial products in exosome-based cancer diagnosis and prognosis.

Academic and industrial groups worldwide have reported technological advances in exosome-based cancer diagnosis and prognosis. However, the potential translation of these emerging technologies for research and clinical settings remains unknown. This work overviews the role of exosomes in cancer diagnosis and prognosis, followed by a survey on emerging exosome technologies, particularly microfluidic advances for the isolation and detection of exosomes in cancer research. The advantages and drawbacks of each of the technologies used for the isolation, detection and engineering of exosomes are evaluated to address their clinical challenges for cancer diagnosis and prognosis. Furthermore, commercial platforms for exosomal detection and analysis are introduced, and their performance and impact on cancer diagnosis and prognosis are assessed. Also, the risks associated with the further development of the next generation of exosome devices are discussed. The outcome of this work could facilitate recognizing deliverable Exo-devices and technologies with unprecedented functionality and predictable manufacturability for the next-generation of cancer diagnosis and prognosis.

A novel tumor inhibitory hybridoma monoclonal antibody with dual specificity for HER3 and HER2.

BACKGROUND: The human epidermal growth factor receptor (HER/ErbB) family-targeted therapies result in a significant improvement in cancer immunotherapy. Monoclonal antibodies (MAb) against HER2 demonstrated a survival benefit for patients; however, drug resistance unavoidably occurs due to the overexpression of HER3, which leads to treatment failure. Effective inhibition of HER3 besides HER2 is thought to be required to overcome resistance and enhance therapeutic efficacy. OBJECTIVE: The present study describes the production and characterization of a novel MAb, designated 1G5D2, which acts as a natural bispecific antibody targeting extracellular domains (ECD) of both HER2 and HER3. METHODS: In this study, 1G5D2 was produced by hybridoma technology against HER3-ECD, and its structural and functional characteristics were studied by various methodologies, including enzyme linked-immunosorbent assays, flow cytometry, immunoblotting, cell signaling, and cell proliferation assays. RESULTS: 1G5D2 specifically binds to both HER2 (subdomain III + IV) and HER3 (subdomain I + II) expressed on tumor cells, and these receptors compete with each other for binding to this MAb. Competition flow cytometry experiments demonstrated that 1G5D2 does not compete with heregulin and recognizes an epitope out of HER3 ligand-binding site. Evaluation of 1G5D2 inhibitory effects in tumor cell lines co-expressing HER2 and HER3 showed that 1G5D2 synergizes with trastuzumab to inhibit both PI3K/AKT and MAPK/ERK pathways and potently downregulates the proliferation of these tumor cells more efficiently than each MAb alone. CONCLUSION: 1G5D2 is the first reported hybridoma antibody, which acts as a natural HER2/HER3 bispecific antibody. It might potentially be a suitable therapeutic candidate for HER2/HER3 overexpressing cancer types.