Characterization of Antimicrobial Activities of Bifidobacterium lactis BB-12 and Their Inhibitory Effect Against Some Foodborne Pathogens.

Bifidobacterium animalis subsp. lactis BB-12, a probiotic, has shown potential to promote health benefits and control pathogens. This study aimed to investigate the effectiveness of BB-12 and its cell-free supernatant (CFS) in inhibiting the growth of Listeria monocytogenes and Salmonella enterica serovar Typhimurium. To assess the antimicrobial activity of BB-12, agar well diffusion, disk diffusion, and minimum inhibitory concentration (MIC) tests were conducted. The bicinchoninic acid (BCA) assay was performed to measure the protein concentration in CFS. The study's results indicated that the BB-12 strain inhibited the pathogens' growth. The disk diffusion test using BB-12 showed inhibitory results ranging from 11 to 14 mm for both bacteria. The agar well diffusion test reported the zone of inhibition ranging from 11.6 to 16 mm for both bacteria. The MIC test was conducted as a confirmatory test, which demonstrated the highest inhibitory zone using 2 McFarland (6 × 108 CFU/mL) concentrations of probiotics on L. monocytogenes (44.98%) and S. Typhimurium (66.41%). The disk diffusion test revealed that the probiotic CFS had a significant inhibitory impact on S. Typhimurium with a 16.6 mm zone of inhibition. The BCA test findings indicated that the 24- and 48-h CFSs exhibited inhibitory properties against infections. Notably, the 24-h CFS, including a protein level of 78.47 µg/mL, demonstrated a more pronounced inhibitory impact on both pathogens. The findings highlight that utilizing the BB-12 strain and its CFS can serve as a viable approach to battle infections, enhancing food safety and public health.

Revolutionizing cancer treatment: the power of bi- and tri-specific T-cell engagers in oncolytic virotherapy.

Bi- or tri-specific T cell engagers (BiTE or TriTE) are recombinant bispecific proteins designed to stimulate T-cell immunity directly, bypassing antigen presentation by antigen-presenting cells (APCs). However, these molecules suffer from limitations such as short biological half-life and poor residence time in the tumor microenvironment (TME). Fortunately, these challenges can be overcome when combined with OVs. Various strategies have been developed, such as encoding secretory BiTEs within OV vectors, resulting in improved targeting and activation of T cells, secretion of key cytokines, and bystander killing of tumor cells. Additionally, oncolytic viruses armed with BiTEs have shown promising outcomes in enhancing major histocompatibility complex I antigen (MHC-I) presentation, T-cell proliferation, activation, and cytotoxicity against tumor cells. These combined approaches address tumor heterogeneity, drug delivery, and T-cell infiltration, offering a comprehensive and effective solution. This review article aims to provide a comprehensive overview of Bi- or TriTEs and OVs as promising therapeutic approaches in the field of cancer treatment. We summarize the cutting-edge advancements in oncolytic virotherapy immune-related genetic engineering, focusing on the innovative combination of BiTE or TriTE with OVs.

Hepatocellular carcinoma (HCC) immunotherapy by anti-PD-1 monoclonal antibodies: A rapidly evolving strategy.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world, with a high relapse rate. Delayed symptom onset observed in 70-80% of patients leads to diagnosis in advanced stages commonly associated with chronic liver disease. Programmed cell death protein 1 (PD-1) blockade therapy has recently emerged as a promising therapeutic option in the clinical management of several advanced malignancies, including HCC, due to the activation of exhausted tumor-infiltrating lymphocytes and improved outcomes of T-cell function. However, many people with HCC do not respond to PD-1 blockade therapy, and the diversity of immune-related adverse events (irAEs) restricts their clinical utility. Therefore, numerous effective combinatory strategies, including combinations with anti-PD-1 antibodies and other therapeutic methods ranging from chemotherapy to targeted therapies, are evolving to improve therapeutic outcomes and evoke synergistic anti-tumor impressions in patients with advanced HCC. Unfortunately, combined therapy may have more side effects than single-agent treatment. Nonetheless, identifying appropriate predictive biomarkers can aid in managing potential immune-related adverse events by distinguishing patients who respond best to PD-1 inhibitors as single agents or in combination strategies. In the present review, we summarize the therapeutic potential of PD-1 blockade therapy for advanced HCC patients. Besides, a glimpse of the pivotal predictive biomarkers influencing a patient's response to anti-PD-1 antibodies will be provided.

Overview of the pre-clinical and clinical studies about the use of CAR-T cell therapy of cancer combined with oncolytic viruses.

BACKGROUND: Cancer is one of the critical issues of the global health system with a high mortality rate even with the available therapies, so using novel therapeutic approaches to reduce the mortality rate and increase the quality of life is sensed more than ever. MAIN BODY: CAR-T cell therapy and oncolytic viruses are innovative cancer therapeutic approaches with fewer complications than common treatments such as chemotherapy and radiotherapy and significantly improve the quality of life. Oncolytic viruses can selectively proliferate in the cancer cells and destroy them. The specificity of oncolytic viruses potentially maintains the normal cells and tissues intact. T-cells are genetically manipulated and armed against the specific antigens of the tumor cells in CAR-T cell therapy. Eventually, they are returned to the body and act against the tumor cells. Nowadays, virology and oncology researchers intend to improve the efficacy of immunotherapy by utilizing CAR-T cells in combination with oncolytic viruses. CONCLUSION: Using CAR-T cells along with oncolytic viruses can enhance the efficacy of CAR-T cell therapy in destroying the solid tumors, increasing the permeability of the tumor cells for T-cells, reducing the disturbing effects of the immune system, and increasing the success chance in the treatment of this hazardous disease. In recent years, significant progress has been achieved in using oncolytic viruses alone and in combination with other therapeutic approaches such as CAR-T cell therapy in pre-clinical and clinical investigations. This principle necessitates a deeper consideration of these treatment strategies. This review intends to curtly investigate each of these therapeutic methods, lonely and in combination form. We will also point to the pre-clinical and clinical studies about the use of CAR-T cell therapy combined with oncolytic viruses.

Enhancement of the Mechanical Properties of Hydroxyapatite/Sulphonated Poly Ether Ether Ketone Treated Layer for Orthopaedic and Dental Implant Application.

The mechanical properties of coated layers are one of the important factors for the long-term success of orthopeadic and dental implants. In this study, the mechanical properties of the porous coated layer were examined via scratch and nanoindentation tests. The effect of compression load on the porous coated layer of sulphonated poly ether ether ketone/Hydroxyapatite was studied to determine whether it changes its mechanical properties. The water contact angle and surface roughness of the compressed coated layer were also measured. The results showed a significant increase in elastic modulus, with mean values ranging from 0.464 GPa to 1.199 GPa (p<0.05). The average scratch hardness also increased significantly from 69.9 MPa to 95.7 MPa after compression, but the surface roughness and wettability decreased significantly (p<0.05). Simple compression enhanced the mechanical properties of the sulphonated poly ether ether ketone/hydroxyapatite coated layer, and the desired mechanical properties for orthopaedic and dental implant application can be achieved.

Functionally graded polymeric materials: A brif review of current fabrication methods and introduction of a novel fabrication method.

The present work reviews the current fabrication methods of the functionally graded polymeric material (FGPM) and introduces a novel fabrication method that is versatile in applications as compared to those of existing used methods. For the first time electrophoresis was used to control the distribution of the tetracycline hydrochloride (TC) in a film made of polylactic acid (PLA), aiming to induce antimicrobial effect on the film prepared. The elemental analysis on the film surface showed that by employing electrophoresis force, higher amount of TC was detected near the top surface of the film. Results also showed that the FGPM samples with higher percentage of the TC on the film surface were highly effective to minimize the growth of Escherichia coli. These findings are useful and important to improve dispersion quality of the particles in the composite material and further enhance its antibacterial property.

Comparing of letrozole versus clomiphene citrate combined with gonadotropins in intrauterine insemination cycles.

BACKGROUND: Clomiphene citrate (CC) an agonist and antagonist of estrogen, is the first line treatment in ovarian stimulation. Anti-estrogenic effect of CC in endometrial thickness and cervical mucus has negative effect on pregnancy rate. Letrozole is an Aromatase Inhibitor has been seen that has acceptable pregnancy rate compared to CC. OBJECTIVE: The aim of this study was to compare the efficacy of letrozole and clomiphene citrate (CC) with gonadotropins for ovarian stimulation in women candidate for intrauterine insemination (IUI). MATERIALS AND METHODS: One hundred sixty patients eligible to IUI therapy enrolled in this study. Patients randomized to two groups: group A (received letrozole-gonadotropin) and group B (received CC-gonadotropin). In group A (n=80) letrozole was given on days 3-7 of the menstrual cycles. In group B clomiphen citrate was given like letrozole combined with human menopausal gonadotropin (hMG) administered every day starting on day 8. Ovulation was triggered with urinary HCG when the leading follicle (s) reached 18 mm in diameter. A single IUI was performed 36-40 hours later. The ovarian stimulation response (E2 levels and number of follicles, clinical pregnancy and endometrial thickness) was primary outcome. RESULTS: Both groups were similar in demographic characteristics. There was a significantly lower peak serum E2 level in the letrozole group compared with CC. (236±86 Vs. 283±106 pg/mL, respectively; p<0.002). The number of mature (>18 mm) preovulatory follicles was significantly higher in CC group than letrozole group (2.2±.68 Vs. 2.02±0.63 respectively; p=0.025). Endometrial thickness measured at the time of hCG administration was significantly higher in letrozole group. (9.08±1.2 mm Vs. 8.1±1.9 mm; p=0.0001). The clinical pregnancy rate was comparable between two groups. Conclusion : Letrozole is a good and cost-effective alternative to CC in IUI cycles.