Clinical curative effect of neoadjuvant chemotherapy combined with immunotherapy and its impact on immunological function and the expression of ER, PR, HER-2 & SATB1 in HER-2-Positive breast cancer patients

Objective: To evaluate the clinical curative effect of neoadjuvant chemotherapy combined with immunotherapy and its impact on immunological function and the expression of ER, PR, HER-2 and SATB1 in HER-2-positive breast cancer patients. Methods: The subjects of study were 80 patients with HER-2-positive breast cancer. Enrolled patients were randomly divided into two groups, with 40 cases in each group at The Fourth Affiliated Hospital of Hebei Medical University from March 2018 from March 2021. Patients in the control group were provided with neoadjuvant chemotherapy using TAC regimen merely; while those in the study group received oral administration of Apatinib Mesylate (500mg/d; three weeks a cycle) on the basis of the TAC regimen. Further comparative analysis was performed focusing on the therapeutic effect and adverse drug reaction rate of the two groups; levels of CD3+, CD4+, CD8+ and CD4+/CD8+ of T lymphocyte subsets in the two groups before and after treatment; as well as the expressions of ER, PR, HER-2 and SATB1 in the two groups before and after treatment. Results: The total response rate was 77.5% and 55% in the study group and the control group, respectively, with an obviously better outcome in the former group than that in the latter group (p=0.03). Meanwhile, the incidence of adverse reactions was 40% in the study group and 45% in the control group, without statistical difference (p=0.65). There were statistically significant differences that the levels of CD3+, CD4+, and CD4+/CD8+ in the study group were significantly higher when compared with those in the control group after treatment (CD3+, p=0.00; CD4+, p=0.02; CD4+/CD8+, p=0.00); while no evident change was observed in the level of CD8+ (p=0.88). After treatment, the positive expression rates of ER, HER-2 and SATB1 were remarkably lower in the study group than those in the control group, showing statistically significant differences (ER, HER-2, p=0.03; SATB1, p=0.02). However, there was no statistically significant difference in the positive expression rate of PR between the study group and the control group (P=0.80). Conclusions: Neoadjuvant chemotherapy combined with immunotherapy has significant effect on the treatment of HER-2-positive breast cancer patients. It can result in the significant enhancement of T lymphocyte function, obvious improvement in the negative converse rates of ER, HER-2 and SATB1, and no evident increase in the adverse drug reactions. The proposed therapeutic approach is safe, effective, and have certain clinical value. doi: https://doi.org/10.12669/pjms.38.3.5199 How to cite this:Chen Z, Sang M, Geng C, Hao W, Jia H. Clinical curative effect of neoadjuvant chemotherapy combined with immunotherapy and its impact on immunological function and the expression of ER, PR, HER-2 and SATB1 in HER-2-Positive breast cancer patients. Pak J Med Sci. 2022;38(3):---------. doi: https://doi.org/10.12669/pjms.38.3.5199 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Potential Physiological and Cellular Mechanisms of Exercise That Decrease the Risk of Severe Complications and Mortality Following SARS-CoV-2 Infection

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has unmasked mankind’s vulnerability to biological threats. Although higher age is a major risk factor for disease severity in COVID-19, several predisposing risk factors for mortality are related to low cardiorespiratory and metabolic fitness, including obesity, cardiovascular disease, diabetes, and hypertension. Reaching physical activity (PA) guideline goals contribute to protect against numerous immune and inflammatory disorders, in addition to multi-morbidities and mortality. Elevated levels of cardiorespiratory fitness, being non-obese, and regular PA improves immunological function, mitigating sustained low-grade systemic inflammation and age-related deterioration of the immune system, or immunosenescence. Regular PA and being non-obese also improve the antibody response to vaccination. In this review, we highlight potential physiological, cellular, and molecular mechanisms that are affected by regular PA, increase the host antiviral defense, and may determine the course and outcome of COVID-19. Not only are the immune system and regular PA in relation to COVID-19 discussed, but also the cardiovascular, respiratory, renal, and hormonal systems, as well as skeletal muscle, epigenetics, and mitochondrial function.

Nanoparticles to Target and Treat Macrophages: The Ockham’s Concept?

Nanoparticles are nanomaterials with three external nanoscale dimensions and an average size ranging from 1 to 1000 nm. Nanoparticles have gained notoriety in technological advances due to their tunable physical, chemical, and biological characteristics. However, the administration of functionalized nanoparticles to living beings is still challenging due to the rapid detection and blood and tissue clearance by the mononuclear phagocytic system. The major exponent of this system is the macrophage. Regardless the nanomaterial composition, macrophages can detect and incorporate foreign bodies by phagocytosis. Therefore, the simplest explanation is that any injected nanoparticle will be probably taken up by macrophages. This explains, in part, the natural accumulation of most nanoparticles in the spleen, lymph nodes, and liver (the main organs of the mononuclear phagocytic system). For this reason, recent investigations are devoted to design nanoparticles for specific macrophage targeting in diseased tissues. The aim of this review is to describe current strategies for the design of nanoparticles to target macrophages and to modulate their immunological function involved in different diseases with special emphasis on chronic inflammation, tissue regeneration, and cancer.

The Effects of In Ovo Injection of Synbiotics on the Early Growth Performance and Intestinal Health of Chicks

In this study, the effects of synbiotic inclusion at the intra-amniotic stage in layer chicks were evaluated with different parameters, such as performance, immunological function, intestinal development, and cecal microflora content. A total of 1,200 eggs with fertile embryos were allocated into four treatment groups. For every treatment, five replicates were used, and 60 eggs were included in each replicate. The following four treatment groups were established: the non-injected group, 0.9% physiological saline injection (saline) group, 1 × 106 CFU/egg Lactobacillus plantarum injection (probiotic) group, and 1 × 106 CFU/egg L. plantarum + 2 mg/egg Astragalus polysaccharide injection (synbiotic) group. In ovo injection was carried out at 18.5 days of incubation. The results showed that in ovo injection of probiotics or synbiotics did not affect the hatching or growth performance of the chicks but significantly increased their feed intake (FI), body weight (BW), and the feed conversion ratio (FCR). Additionally, in ovo injection of synbiotics enhanced the levels of serum interleukin-2 (IL-2), interferon-γ (IFN-γ), and secretory immunoglobulin A (SIgA) in intestinal lavage fluid and the histomorphological development of the small intestine. Our results also indicated that intra-amniotic synbiotic injection significantly increased Lactobacillus and Bifidobacterium colonization while decreasing the relative abundance of Escherichia coli in the chicken cecum (P < 0.05). In summary, in ovo injection of synbiotics had positive impacts on the performance, immunological function, gut development, and microbiota of growing chicks.

Ubiquitous membrane-bound DNase activity in podosomes and invadopodia

Podosomes and invadopodia, collectively termed invadosomes, are adhesive and degradative membrane structures formed in many types of cells and are well known for recruiting various proteases. However, another major class of degradative enzymes, deoxyribonuclease (DNase), remains unconfirmed and not studied in invadosomes. Here, using surface-immobilized nuclease sensor (SNS), we demonstrated that invadosomes recruit DNase to their core regions, which degrade extracellular double-stranded DNA. We further identified the DNase as GPI-anchored membrane-bound DNase X. DNase recruitment is ubiquitous and consistent in invadosomes of all tested cell types. DNase activity exhibits within a minute after actin nucleation, functioning concomitantly with protease in podosomes but preceding it in invadopodia. We further showed that macrophages form DNase-active podosome rosettes surrounding bacteria or micropatterned antigen islets, and the podosomes directly degrade bacterial DNA on a surface, exhibiting an apparent immunological function. Overall, this work reports DNase in invadosomes for the first time, suggesting a richer arsenal of degradative enzymes in invadosomes than known before.

Notch2-mediated plasticity between marginal zone and follicular B cells

Follicular B (FoB) and marginal zone B (MZB) cells are functionally and spatially distinct mature B cell populations in the spleen, originating from a Notch2-dependent fate decision after splenic influx of immature transitional B cells. In the B cell follicle, a Notch2-signal is provided by DLL-1-expressing fibroblasts. However, it is unclear whether FoB cells, which are in close contact with these DLL-1 expressing fibroblasts, can also differentiate to MZB cells if they receive a Notch2-signal. Here, we show induced Notch2IC-expression in FoB cells re-programs mature FoB cells into bona fide MZB cells as is evident from the surface phenotype, localization, immunological function and transcriptome of these cells. Furthermore, the lineage conversion from FoB to MZB cells occurs in immunocompetent wildtype mice. These findings demonstrate plasticity between mature FoB and MZB cells that can be driven by a singular signaling event, the activation of Notch2.

15-Lipoxygenase-2 Deficiency Induces a Dysfunction in Macrophages That Can Be Restored by Salidroside

15-Lipoxygenase-2(15-LOX-2) is thought to regulate inflammation and immunological function however, its mechanisms of action are still unclear. Furthermore, it has been reported that salidroside has anti inflammatory properties , but its role in macrophage function has not been understood yet In this study, we aimed to determine how 15-LOX-2 expression level s affect the function of macrophages and the effect of salidroside on 15-LOX-2 deficient macrophages We used multiple functional genetic strategies to determine 15-LOX-2 function in macrophages. 15-LOX-2 deficiency promotes phagocytosis and proliferation of macrophages and impairs their apoptosis Mechanistically, t he expression levels of cyclophilinB (CypB) were upregulated in 15-LOX-2 deficient Ana 1 macrophages, whereas those of caspase 3 were down regulated. Furthermore, RNA-seq analysis showed that inflammation, complement, and TNF-α signaling pathway s were all activated in 15-LOX-2 deficient Ana 1 macrophages. Treatment of 15-LOX-2 deficient macrophages with salidroside, a natural product derived from Rhodiola species, effectively reversed the effects of 15-LOX-2 deficiency on caspase 3 and CypB levels, as well as on apoptosis and proliferation. In conclusion, our study shows that there is a newly identified link between 15-LOX-2 deficiency and salidroside in regulating macrophage survival, proliferation, and function. Salidroside may be a promising therapeutic strategy for treating inflammation related diseases resulting from 15-LOX-2 deficiency.

Endorphinergic Enhancement Attenuation of Post-Traumatic Stress Disorder (PTSD) via Activation of Neuro-immunological Function in the Face of a Viral Pandemic

Introduction: Polymorphic gene variants, particularly the genetic determinants of low dopamine function (hy-podopaminergia), are known to associate with Substance Use Disorder and a predisposition to PTSD. Addiction research and molecular genetic applied technologies supported by the National Institutes of Health (NIH) have revealed the com-plex functions of brain reward circuitry and its crucial role in addiction and PTSD symptomatology. Discussion: It is noteworthy that Israeli researchers compared mice with a normal immune system with mice lacking adaptive immunity and found that the incidence of PTSD increased several-fold. It is well established that raising endor-phinergic function increases immune response significantly. Along these lines, Blum’s work has shown that D-Phenylalanine (DPA), an enkephalinase inhibitor, increases brain endorphins in animal models and reduces stress in hu-mans. Enkephalinase inhibition with DPA treats Post Traumatic Stress Disorder (PTSD) by restoring endorphin function. The Genetic Addiction Risk Score (GARS) can characterize relevant phenotypes, genetic risk for stress vulnerability vs. resilience. GARS could be used to pre-test military enlistees for adaptive immunity or as part of PTSD management with customized neuronutrient supplementation upon return from deployment. Conclusion: Based on GARS values, with particular emphasis on enhancing immunological function, pro-dopamine regu-lation may restore dopamine homeostasis. Recognition of the immune system as a “sixth sense” and assisting adaptive immunity with Precision Behavioral Management (PBM), accompanied by other supportive interventions and therapies, may shift the paradigm in treating stress disorders.