Restoring the epigenetic landscape of lung microbiome: potential therapeutic approach for chronic respiratory diseases.

BACKGROUND: Chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and bronchiectasis, present significant threats to global health. Recent studies have revealed the crucial role of the lung microbiome in the development of these diseases. Pathogens have evolved complex strategies to evade the immune response, with the manipulation of host cellular epigenetic mechanisms playing a pivotal role. There is existing evidence regarding the effects of Pseudomonas on epigenetic modifications and their association with pulmonary diseases. Therefore, this study aims to directly assess the connection between Pseudomonas abundance and chronic respiratory diseases. We hope that our findings will shed light on the molecular mechanisms behind lung pathogen infections. METHODS: We analyzed data from 366 participants, including individuals with COPD, acute exacerbations of COPD (AECOPD), bronchiectasis, and healthy individuals. Previous studies have given limited attention to the impact of Pseudomonas on these groups and their comparison with healthy individuals. Two independent datasets from different ethnic backgrounds were used for external validation. Each dataset separately analyzed bacteria at the genus level. RESULTS: The study reveals that Pseudomonas, a bacterium, was consistently found in high concentrations in all chronic lung disease datasets but it was present in very low abundance in the healthy datasets. This suggests that Pseudomonas may influence cellular mechanisms through epigenetics, contributing to the development and progression of chronic respiratory diseases. CONCLUSIONS: This study emphasizes the importance of understanding the relationship between the lung microbiome, epigenetics, and the onset of chronic pulmonary disease. Enhanced recognition of molecular mechanisms and the impact of the microbiome on cellular functions, along with a better understanding of these concepts, can lead to improved diagnosis and treatment.

Induction of Skin Allograft Chimerism by Pharmacological Mobilization of Endogenous Bone Marrow-Derived Stem Cells.

Skin substitutes including allografts remain a standard therapeutic approach to promote healing of both acute and chronic large wounds. However, none have resulted in the regrowth of lost and damaged tissues and scarless wound healing. Here, we demonstrate skin allograft chimerism and repair through the mobilization of endogenous bone marrow-derived stem and immune cells in rats and swine. We show that pharmacological mobilization of bone marrow stem cells and immune cells into the circulation promotes host repopulation of skin allografts and restoration of the skin's normal architecture without scarring and minimal contracture. When skin allografts from DA rats are transplanted into GFP transgenic Lewis recipients with a combination of AMD3100 and low-dose FK506 (AF) therapy, host-derived GFP-positive cells repopulate and/or regenerate cellular components of skin grafts including epidermis and hair follicles and the grafts become donor-host chimeric skin. Using AF combination therapy, burn wounds with skin allografts were healed by newly regenerated chimeric skin with epidermal appendages and pigmentation and without contracture in swine.

The Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE): protocol for a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Inflammation is a key mediator in the development and progression of the atherosclerotic disease process as well as its resultant complications, like myocardial infarction (MI), stroke and cardiovascular (CV) death, and is emerging as a novel treatment target. Trials involving anti-inflammatory medications have demonstrated outcome benefit in patients with known CV disease. In this regard, colchicine appears to hold great promise. However, there are potential drawbacks to colchicine use, as some studies have identified an increased risk of infection, and a non-significant trend for increased all-cause mortality. Thus, a more thorough understanding of the underlying mechanism of action of colchicine is needed to enable a better patient selection for this novel CV therapy. OBJECTIVE: The primary objective of the Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE) trial is to assess the effect of colchicine on vascular inflammation in the carotid arteries and ascending aorta measured with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with type 2 diabetes mellitus (T2DM) or pre-diabetes who have experienced a recent vascular event (acute coronary syndrome (ACS)/MI, transient ischaemic attack (TIA) or stroke). Secondary objectives include determining colchicine's effect on inflammatory biomarkers (high-sensitivity C reactive protein (hs-CRP) and interleukin-6 (IL-6)). Additionally, we will assess if baseline inflammation imaging or biomarkers are associated with a treatment response to colchicine determined by imaging. Exploratory objectives will look at: (1) the difference in the inflammatory response to colchicine in patients with coronary events compared with patients with cerebral events; (2) the difference in the inflammatory response to colchicine in different vascular beds; (3) the relationship of FDG-PET imaging markers with serum biomarkers and (4) assessment of quality-of-life changes. METHODS AND DESIGN: CADENCE is a multicentre, prospective, randomised, double-blinded, placebo-controlled study to determine the effect of colchicine on arterial inflammation as assessed with imaging and circulatory biomarkers, specifically carotid arteries and aortic FDG uptake as well as hs-CRP and IL-6 among others. Patients with T2DM or pre-diabetes who have recently experienced a CV event (within 30-120 days after an ACS (ie, ST-elevation MI (STEMI) or non-STEMI)) or TIA/stroke with documented large vessel atherosclerotic disease will be randomised to treatment with either colchicine 0.6 mg oral daily or placebo. Participants will undergo baseline clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan of the ascending aorta and left and right carotid arteries. Patients will undergo treatment for 6 months and have repeat clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan at the conclusion of the study. The primary outcome will be the change in the maximum target to background ratio (TBRmax) in the ascending aorta (or carotid arteries) from baseline to follow-up on FDG PET/CT imaging. DISCUSSION: Colchicine is an exciting potential new therapy for CV risk reduction. However, its use is associated with side effects and greater understanding of its underlying mechanism of action is needed. Importantly, the current study will determine whether its anti-inflammatory action is an indirect systemic effect, or a more local plaque action that decreases inflammation. The results will also help identify patients who will benefit most from such therapy. TRIAL REGISTRATION NUMBER: NCT04181996.

Association between single-nucleotide polymorphism of cytokines genes and chronic obstructive pulmonary disease: A systematic review and meta-analysis.

Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease with high morbidity and mortality rates worldwide. Cytokines, which are the main regulators of immune responses, play crucial roles in inflammatory diseases such as COPD. Moreover, certain genetic variations can alter cytokine expression, and changes in cytokine level or function can affect disease susceptibility. Therefore, investigating the association between genetic variations and disease progression can be useful for prevention and treatment. Several studies have explored the association between common genetic variations in cytokine genes and COPD susceptibility. In this study, we summarized the reported studies and, where possible, conducted a systematic review and meta-analysis to evaluate the genetic association between various cytokines and COPD pathogenesis. We extracted relevant articles from PubMed and Google Scholar databases using a standard systematic search strategy. We included a total of 183 studies from 78 separate articles that evaluated 50 polymorphisms in 12 cytokine genes in this study. Our analysis showed that among all reported cytokine polymorphisms (including TNF-α, TGF-ß, IL1, IL1RN, IL4, IL4R, IL6, IL10, IL12, IL13, IL17, IL18, IL27, and IL33), only four variants, including TNF-α-rs1800629, TGF-ß1-rs6957, IL13-rs1800925, and IL6-rs1800796, were associated with the risk of COPD development. This updated meta-analysis strongly supports the association of TNF-α-rs1800629, TGF-ß1-rs6957, IL13-rs1800925, and IL6-rs1800796 variants with a high risk of COPD.

Autophagy, a critical element in the aging male reproductive disorders and prostate cancer: a therapeutic point of view.

Autophagy is a highly conserved, lysosome-dependent biological mechanism involved in the degradation and recycling of cellular components. There is growing evidence that autophagy is related to male reproductive biology, particularly spermatogenic and endocrinologic processes closely associated with male sexual and reproductive health. In recent decades, problems such as decreasing sperm count, erectile dysfunction, and infertility have worsened. In addition, reproductive health is closely related to overall health and comorbidity in aging men. In this review, we will outline the role of autophagy as a new player in aging male reproductive dysfunction and prostate cancer. We first provide an overview of the mechanisms of autophagy and its role in regulating male reproductive cells. We then focus on the link between autophagy and aging-related diseases. This is followed by a discussion of therapeutic strategies targeting autophagy before we end with limitations of current studies and suggestions for future developments in the field.

A phase I, first-in-human study to evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics of MRG-001 in healthy subjects.

Preclinical studies demonstrate that pharmacological mobilization and recruitment of endogenous bone marrow stem cells and immunoregulatory cells by a fixed-dose drug combination (MRG-001) improves wound healing, promotes tissue regeneration, and prevents allograft rejection. In this phase I, first-in-human study, three cohorts receive subcutaneous MRG-001 or placebo, every other day for 5 days. The primary outcome is safety and tolerability of MRG-001. Fourteen subjects received MRG-001 and seven received a placebo. MRG-001 is safe over the selected dose range. There are no clinically significant laboratory changes. The intermediate dose group demonstrates the most significant white blood cell, stem cell, and immunoregulatory cell mobilization. PBMC RNA sequencing and gene set enrichment analysis reveal 31 down-regulated pathways in the intermediate MRG-001 dose group compared with no changes in the placebo group. MRG-001 is safe across all dose ranges. MRG-001 may be a clinically useful therapy for immunoregulation and tissue regeneration (ClinicalTrials.gov: NCT04646603).

Exploring Co-occurrence patterns and microbial diversity in the lung microbiome of patients with non-small cell lung cancer.

BACKGROUND: It has been demonstrated in the literature that a dysbiotic microbiome could have a negative impact on the host immune system and promote disease onset or exacerbation. Co-occurrence networks have been widely adopted to identify biomarkers and keystone taxa in the pathogenesis of microbiome-related diseases. Despite the promising results that network-driven approaches have led to in various human diseases, there is a dearth of research pertaining to key taxa that contribute to the pathogenesis of lung cancer. Therefore, our primary goal in this study is to explore co-existing relationships among members of the lung microbial community and any potential gained or lost interactions in lung cancer. RESULTS: Using integrative and network-based approaches, we integrated four studies assessing the microbiome of lung biopsies of cancer patients. Differential abundance analyses showed that several bacterial taxa are different between tumor and tumor-adjacent normal tissues (FDR adjusted p-value < 0.05). Four, fifteen, and twelve significantly different associations were found at phylum, family, and genus levels. Diversity analyses suggested reduced alpha diversity in the tumor microbiome. However, beta diversity analysis did not show any discernible pattern between groups. In addition, four distinct modules of bacterial families were detected by the DBSCAN clustering method. Finally, in the co-occurrence network context, Actinobacteria, Firmicutes, Bacteroidetes, and Chloroflexi at the phylum level and Bifidobacterium, Massilia, Sphingobacterium, and Ochrobactrum at the genus level showed the highest degree of rewiring. CONCLUSIONS: Despite the absence of statistically significant differences in the relative abundance of certain taxa between groups, it is imperative not to overlook them for further exploration. This is because they may hold pivotal central roles in the broader network of bacterial taxa (e.g., Bifidobacterium and Massilia). These findings emphasize the importance of a network analysis approach for studying the lung microbiome since it could facilitate identifying key microbial taxa in lung cancer pathogenesis. Relying exclusively on differentially abundant taxa may not be enough to fully grasp the complex interplay between lung cancer and the microbiome. Therefore, a network-based approach can offer deeper insights and a more comprehensive understanding of the underlying mechanisms.

The association between Vitamin D deficiency and fibrocystic breast disorder.

BACKGROUND: The role of deficiency of vitamin D in a wide range of human cancer, including breast cancer, has been proven, but its role in benign breast diseases remains unknown. This study aimed to determine the prevalence of vitamin D deficiency in patients with fibrocystic breast (FB) disease. METHODS: First, the hospital prevalence of fibrocystic breast was determined by a cross-sectional study. Then, patients were divided into two groups by a case-control study; women with confirmed fibrocystic breasts based on breast pain, physical examination, and ultrasonography were included as a case group (N=48) and age-matched women without fibrocystic breasts were also included as a control group (N=48). After recording the demographic and gynecological characteristics and exposure to the sun, gynecological records, and family history of fibrocystic breast, the blood sample was taken to determine vitamin D. Data were analyzed by Stata software. RESULTS: The result indicated that the studied groups had significant differences in regards to weight, breast pain, the severity of breast pain, breast heaviness, family history of fibrocystic breast, history of breast disease, caffeine consumption, and exposure to sunlight (p <0.05), but did not show significant differences based on age, occupation, education, gynecological history, diabetes mellitus, hypertension, obesity and hypothyroidism, vegetable, fast food, and dairy products consumption. The frequency of vitamin D deficiency in the case group was 45.8%, and in the control group, it was 20.8%, and there was a statistically significant difference (p <0.05). CONCLUSION: Vitamin D deficiency is more common in women with fibrocystic breast disease and may play a role in the development of the disease.

cAMP-PDE signaling in COPD: Review of cellular, molecular and clinical features.

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death among non-contagious diseases in the world. PDE inhibitors are among current medicines prescribed for COPD treatment of which, PDE-4 family is the predominant PDE isoform involved in hydrolyzing cyclic adenosine monophosphate (cAMP) that regulates the inflammatory responses in neutrophils, lymphocytes, macrophages and epithelial cells The aim of this study is to investigate the cellular and molecular mechanisms of cAMP-PDE signaling, as an important pathway in the treatment management of patients with COPD. In this review, a comprehensive literature review was performed about the effect of PDEs in COPD. Generally, PDEs are overexpressed in COPD patients, resulting in cAMP inactivation and decreased cAMP hydrolysis from AMP. At normal amounts, cAMP is one of the essential agents in regulating metabolism and suppressing inflammatory responses. Low amount of cAMP lead to activation of downstream inflammatory signaling pathways. PDE4 and PDE7 mRNA transcript levels were not altered in polymorphonuclear leukocytes and CD8 lymphocytes originating from the peripheral venous blood of stable COPD subjects compared to healthy controls. Therefore, cAMP-PDE signaling pathway is one of the most important signaling pathways involved in COPD. By examining the effects of different drugs in this signaling pathway critical steps can be taken in the treatment of this disease.

Determination of metal(oids) in different traditional flat breads distributed in Isfahan city, Iran: Health risk assessment study by latin hypercube sampling.

This survey was conducted to assess the metal(oids) content in 93 samples of bread, including barbari, lavash, and tafton, using inductive couple plasma/optical emission spectroscopy (ICP-OES) method and atomic absorption spectroscopy (AAS). The amounts of measured element were compared with the permissible limit set for bread by FAO/WHO and Iranian National Standardization Organization (INSO). The limit of detection (LOD) was ranged from 6.6 × 10-5 to 2.1 × 10-2 mg l-1 with recoveries ranged from 92% to 102%. The average concentrations of aluminum (Al), arsenic (As), boron (B), cadmium (Cd), iron (Fe), mercury (Hg), magnesium (Mg), sodium (Na), lead (Pb), and zinc (Zn) in bread were 29.88 ±â€¯8, 0.03 ±â€¯0.004, 12.77 ±â€¯3.70, 0.01 ±â€¯0.006, 34.16 ±â€¯8.95, 0.01 ±â€¯0.008, 346.07 ±â€¯36.08, 3314.81 ±â€¯317.19, 0.24 ±â€¯0.11, and 19.65 ±â€¯4.66 mg Kg-1, respectively. Amounts of As, Cd, Hg, Mg, Pb, and Zn were lower, and those of Al, Fe, and Na were higher than the permissible limits defined by FAO/WHO. The Latin Hyper Cube (LHC) sampling results revealed that children were exposed to higher non-carcinogenic risk and adults were more threatened by carcinogenic risk. It is recommended to control the entrance of metals in bread in the farm-to-fork chain in order to prevent probable future health challenges.

Nociceptor neurons affect cancer immunosurveillance.

Solid tumours are innervated by nerve fibres that arise from the autonomic and sensory peripheral nervous systems1-5. Whether the neo-innervation of tumours by pain-initiating sensory neurons affects cancer immunosurveillance remains unclear. Here we show that melanoma cells interact with nociceptor neurons, leading to increases in their neurite outgrowth, responsiveness to noxious ligands and neuropeptide release. Calcitonin gene-related peptide (CGRP)-one such nociceptor-produced neuropeptide-directly increases the exhaustion of cytotoxic CD8+ T cells, which limits their capacity to eliminate melanoma. Genetic ablation of the TRPV1 lineage, local pharmacological silencing of nociceptors and antagonism of the CGRP receptor RAMP1 all reduced the exhaustion of tumour-infiltrating leukocytes and decreased the growth of tumours, nearly tripling the survival rate of mice that were inoculated with B16F10 melanoma cells. Conversely, CD8+ T cell exhaustion was rescued in sensory-neuron-depleted mice that were treated with local recombinant CGRP. As compared with wild-type CD8+ T cells, Ramp1-/- CD8+ T cells were protected against exhaustion when co-transplanted into tumour-bearing Rag1-deficient mice. Single-cell RNA sequencing of biopsies from patients with melanoma revealed that intratumoral RAMP1-expressing CD8+ T cells were more exhausted than their RAMP1-negative counterparts, whereas overexpression of RAMP1 correlated with a poorer clinical prognosis. Overall, our results suggest that reducing the release of CGRP from tumour-innervating nociceptors could be a strategy to improve anti-tumour immunity by eliminating the immunomodulatory effects of CGRP on cytotoxic CD8+ T cells.

Insight into Nano-chemical Enhanced Oil Recovery from Carbonate Reservoirs Using Environmentally Friendly Nanomaterials.

The use of nanoparticles (NPs) in enhanced oil recovery (EOR) processes is very effective in reducing the interfacial tension (IFT) and surface tension (ST) and altering the wettability of reservoir rocks. The main purpose of this study was to use the newly synthesized nanocomposites (KCl/SiO2/Xanthan NCs) in EOR applications. Several analytical techniques including X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscope (SEM) were applied to confirm the validity of the synthesized NCs. From the synthesized NCs, nanofluids were prepared at different concentrations of 100-2000 ppm and characterized using electrical conductivity, IFT, and ST measurements. From the obtained results, it can be observed that 1000 ppm is the optimal concentration of the synthesized NCs that had the best performance in EOR applications. The nanofluid with 1000 ppm KCl/SiO2/Xanthan NCs enabled reducing the IFT and ST from 33 and 70 to 29 and 40 mN/m, respectively. However, the contact angle was highly decreased under the influence of the same nanofluid to 41° and the oil recovery improved by an extra 17.05% OOIP. To sum up, KCl/SiO2/Xanthan NCs proved highly effective in altering the wettability of rocks from oil-wet to water-wet and increasing the cumulative oil production.

Development of an online cancer data collection and processing tool for population-based cancer registries in a low-resource setting: The CanDCap experience from Golestan, Iran.

BACKGROUND: Golestan Population-based Cancer Registry (GPCR) with more than 15-years experiences developed an in-house online software called Cancer Data Collection and Processing (CanDCap) to improve its data collection operations from the conventional offline method to new online method. We aimed to report the methods and framework that GPCR applied to design and implementation of the CanDCap. METHODS: CanDCap was designed based on International Agency for Research on Cancer (IARC) protocols and standards and according to the GPCR workflow. CanDCap has two parts including a web-based online part for data collection and a windows-based part for data processing consisting of quality control and deduplication of repeated records. Questionnaire for User Interface Satisfaction (QUIS) was used in order to assess user interaction satisfaction. RESULTS: CanDCap was implemented in 2018 and could improve the quality of the GPCR data during its first three years of activity (2018-2020), during which about 9,000 records were registered. The coverage for optional items including national ID, father name, address and telephone number were improved from 23 %, 32 %, 83 % and 82 % in conventional offline method (2015-2017) to 83 %, 81 %, 87 %, and 90 % after using the CanDCap (2018-2020), respectively. The timeliness was also improved from 4 years to 2 years. Overall, user interaction satisfaction was acceptable (7.8 out of 9). CONCLUSION: CanDCap could resulted in improvement in data quality and timeliness of the GPCR as a cancer registry unit with limited resources. It has the potential to be considered as a model for population-based cancer registries in lower-resource settings.

Polyphenols and atherosclerosis: A critical review of clinical effects on LDL oxidation.

Atherosclerosis is a major etiology of cardiovascular disease that causes considerable mortality. Oxidized low-density lipoprotein (oxLDL) is a fundamental attributor to atherosclerosis. Therefore, there seems to be an essential place for antioxidant therapy besides the current treatment protocols for coronary heart disease. Polyphenols are a class of compounds with substantial antioxidant properties that have shown the ability to reduce LDL oxidation in preclinical studies. However, clinical evidence has not been as conclusive although offering many promising signs. This review aims to examine the trials that have evaluated how dietary intake of polyphenols in different forms might influence the oxidation of LDL. Lowering the circulating cholesterol, incorporation into LDL particles, and enhancing systemic antioxidant activity are among the main mechanisms of action for polyphenols for lowering oxLDL. On the other hand, the population under study significantly affects the impact on oxLDL, as the type of the supplement and phenolic content. To conclude, although the polyphenols might decrease inflammation and enhance endothelial function via lowering oxLDL, there are still many gaps in our knowledge that need to be filled with further high-quality studies.

Teasing Out the Interplay Between Natural Killer Cells and Nociceptor Neurons.

Somatosensory neurons have evolved to detect noxious stimuli and activate defensive reflexes. By sharing means of communication, nociceptor neurons also tune host defenses by controlling the activity of the immune system. The communication between these systems is mostly adaptive, helping to protect homeostasis, it can also lead to, or promote, the onset of chronic diseases. Both systems co-evolved to allow for such local interaction, as found in primary and secondary lymphoid tissues and mucosa. Recent studies have demonstrated that nociceptors directly detect and respond to foreign antigens, immune cell-derived cytokines, and microbes. Nociceptor activation not only results in pain hypersensitivity and itching, but lowers the nociceptor firing threshold, leading to the local release of neuropeptides. The peptides that are produced by, and released from, the peripheral terminals of nociceptors can block the chemotaxis and polarization of lymphocytes, controlling the localization, duration, and type of inflammation. Recent evidence shows that sensory neurons interact with innate immune cells via cell-cell contact, for example, engaging group 2D (NKG2D) receptors on natural killer (NK) cells. Given that NK cells express the cognate receptors for various nociceptor-produced mediators, it is conceivable that nociceptors use neuropeptides to control the activity of NK cells. Here, we devise a co-culture method to study nociceptor neuron-NK cell interactions in a dish. Using this approach, we found that lumbar nociceptor neurons decrease NK cell cytokine expression. Overall, such a reductionist method could be useful to study how tumor-innervating neurons control the anticancer function of NK cells and how NK cells control the elimination of injured neurons.

Protective and therapeutic effects of Scutellaria baicalensis and its main active ingredients baicalin and baicalein against natural toxicities and physical hazards: a review of mechanisms.

OBJECTIVES: Scutellaria baicalensis (SB) has been traditionally used to combat a variety of conditions ranging from ischemic heart disease to cancer. The protective effects of SB are due to the action of two main flavonoids baicalin (BA) and baicalein (BE). This paper aimed to provide a narrative review of the protective and antidotal effects of SB and its main constituents against natural toxicities and physical hazards. EVIDENCE ACQUISITION: Scientific databases Medline, Scopus, and Web of Science were thoroughly searched, based on different keywords for in vivo, in vitro and clinical studies which reported protective or therapeutic effects of SB or its constituents in natural and physical toxicities. RESULTS: Numerous studies have reported that treatment with BE, BA, or total SB extract prevents or counteracts the detrimental toxic effects of various natural compounds and physical hazards. The toxic agents include mycotoxins, lipopolysaccharide, multiple plants and animal-derived substances as well as physical factors which negatively affected vital organs such as CNS, liver, kidneys, lung and heart. Increasing the expression of radical scavenging enzymes and glutathione content as well as inhibition of pro-inflammatory cytokines and pro-apoptotic mediators were important mechanisms of action. CONCLUSION: Different studies on the Chinese skullcap have exhibited that its total root extract, BA or BE can act as potential antidotes or protective agents against the damage induced by natural toxins and physical factors by alleviating oxidative stress and inflammation. However, the scarcity of high-quality clinical evidence means that further clinical studies are required to reach a more definitive conclusion.

Scutellaria baicalensis and its constituents baicalin and baicalein as antidotes or protective agents against chemical toxicities: a comprehensive review.

Scutellaria baicalensis (SB), also known as the Chinese skullcap, has a long history of being used in Chinese medicine to treat a variety of conditions ranging from microbial infections to metabolic syndrome and malignancies. Numerous studies have reported that treatment with total SB extract or two main flavonoids found in its root and leaves, baicalin (BA) and baicalein (BE), can prevent or alleviate the detrimental toxic effects of exposure to various chemical compounds. It has been shown that BA and BE are generally behind the protective effects of SB against toxicants. This paper aimed to review the protective and therapeutic effects of SB and its main components BA and BE against chemical compounds that can cause intoxication after acute or chronic exposure and seriously affect different vital organs including the brain, heart, liver, and kidneys. In this review paper, we had a look into a total of 221 in vitro and in vivo studies from 1995 to 2021 from the scientific databases PubMed, Scopus, and Web of Science which reported protective or therapeutic effects of BA, BE, or SB against drugs and chemicals that one might be exposed to on a professional or accidental basis and compounds that are primarily used to simulate disease models. In conclusion, the protective effects of SB and its flavonoids can be mainly attributed to increase in antioxidants enzymes, inhibition of lipid peroxidation, reduction of inflammatory cytokines, and suppression of apoptosis pathway.

Causal Path of COPD Progression-Associated Genes in Different Biological Samples.

Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease with pulmonary and extra-pulmonary complications. Due to the disease's systemic nature, many investigations investigated the genetic alterations in various biological samples. We aimed to infer causal genes in COPD's pathogenesis in different biological samples using elastic-net logistic regression and the Structural Equation Model. Samples of small airway epithelial cells, bronchoalveolar lavage macrophages, lung tissue biopsy, sputum, and blood samples were selected (135, 70, 235, 143, and 226 samples, respectively). Elastic-net Logistic Regression analysis was implemented to identify the most important genes involved in COPD progression. Thirty-three candidate genes were identified as essential factors in the pathogenesis of COPD and regulation of lung function. Recognized candidate genes in small airway epithelial (SAE) cells have the highest area under the ROC curve (AUC = 97%, SD = 3.9%). Our analysis indicates that macrophages and epithelial cells are more influential in COPD progression at the transcriptome level.

Monoclonal antibodies for the treatment of acute lymphocytic leukemia: A literature review.

BACKGROUND: Acute lymphocytic leukemia (ALL) is a type of blood cancer that is more prevalent in children. Several treatment methods are available for ALL, including chemotherapy, upfront treatment regimens, and pediatric-inspired regimens for adults. Monoclonal antibodies (Mabs) are the novel Food and Drug Administration (FDA) approved remedies for the relapsed/refractory (R/R) adult ALL. In this article, we aimed to review studies that investigated the efficacy and safety of Mabs on ALL. METHODS: We gathered studies through a complete search with all proper related keywords in ISI Web of Science, SID, Scopus, Google Scholar, Science Direct, and PubMed for English language publications up to 2020. RESULTS: The most commonly studied Mabs for ALL therapies are CD-19, CD-20, CD-22, and CD-52. The best results have been reported in the administration of blinatumomab, rituximab, ofatumumab, and inotuzumab with acceptable low side effects. CONCLUSION: Appling personalized approach for achieving higher efficacy is one of the most important aspects of treatment. Moreover, we recommend that the wide use of these Mabs depends on designing further cost-effectiveness trials in this field.

A Post-Marketing Surveillance Study to Evaluate the Safety Profile of AlvotereⓇ (Docetaxel) in Iranian Patients Diagnosed with Different Types of Cancers Receiving Chemotherapy.

BACKGROUND: Docetaxel is a clinically well established antimitotic chemotherapy medication. Labeled docetaxel indications are breast cancer, gastric cancer, head and neck cancer, non-small cell lung cancer, and prostate cancer. OBJECTIVE: This is a Phase IV study to evaluate the safety profile of docetaxel (Alvotere; NanoAlvand, Iran) in Iranian patients diagnosed with different types of cancers receiving chemotherapy regimens with docetaxel. METHODS: Patients who received Alvotere as a part of their chemotherapy regimen were enrolled in this Phase IV, observational, multicenter, open-label study. Alvotere was administrated as a single agent or in combination with other chemotherapy agents. Safety parameters in each cycle were assessed, and the related data were recorded in booklets. FINDINGS: A total of 411 patients with different types of cancers were enrolled from 25 centers in Iran. The most common malignancies among participants were breast cancer (49.88%), followed by gastric cancer (22.63%). Participants' mean age was 53.33 years, and the mean total dose used in each cycle was 132 mg. According to the results, 341 patients experienced at least 1 adverse event, that the most common was alopecia (41.12%). In total, 92 (22.38%) patients had at least 1 adverse event of grade 3 or 4, and 25 (6.08%) patients showed 54 serious adverse events, which the causality assessment for all was possibly related to Alvotere. There was a significant difference between men and women in the incidence of skin and subcutaneous tissue disorders (55.63% in women vs 41.73% in men; P = 0.009). Also, the incidence of gastrointestinal disorders, nervous system disorders, skin and subcutaneous tissue disorders, hepatic enzymes increase, and fluid retention was significantly higher (P < 0.05) in patients receiving anthracyclines in their chemotherapy regimens. CONCLUSIONS: The findings of this open-label, observational, multicenter, postmarketing surveillance showed that Alvotere appears to have an acceptable safety profile in Iranian cancer patients receiving chemotherapeutic regimens. (Curr Ther Res Clin Exp. 2022; 82:XXX-XXX) © 2022 Elsevier HS Journals, Inc.