Surface-enhanced Raman spectroscopy of the filtrate portions of the blood serum samples of breast cancer patients obtained by using 30 kDa filtration device.

Raman spectroscopy is reliable tool for analyzing and exploring early disease diagnosis related to body fluids, such as blood serum, which contain low molecular weight fraction (LMWF) and high molecular weight fraction (HMWF) proteins. The disease biomarkers consist of LMWF which are dominated by HMWF hence their analysis is difficult. In this study, in order to overcome this issue, centrifugal filter devices of 30 kDa were used to obtain filtrate and residue portions obtained from whole blood serum samples of control and breast cancer diagnosed patients. The filtrate portions obtained in this way are expected to contain the marker proteins of breast cancer of the size below this filter size. These may include prolactin, Microphage migration inhabitation factor (MIF), γ-Synuclein, BCSG1, Leptin, MUC1, RS/DJ-1 present in the centrifuged blood serum (filtrate portions) which are then analyzed by the SERS technique to recognize the SERS spectral characteristics associated with the progression of breast cancer in the samples of different stages as compared to the healthy ones. The key intention of this study is to achieve early-stage breast cancer diagnosis through the utilization of Surface Enhanced Raman Spectroscopy (SERS) after the centrifugation of healthy and breast cancer serum samples with Amicon ultra-filter devices of 30 kDa. The silver nanoparticles with high plasmon resonance are used as a substrate for SERS analysis. Principal Component Analysis (PCA) and Partial Least Discriminant Analysis (PLS-DA) models are utilized as spectral classification tools to assess and predict rapid, reliable, and non-destructive SERS-based analysis. Notably, they were particularly effective in distinguishing between different SERS spectral groups of the cancerous and non-cancerous samples. By comparing all these spectral data sets to each other PLSDA shows the 79 % accuracy, 76 % specificity, and 81 % sensitivity in samples with AUC value of AUC = 0.774 SERS has proven to be a valuable technique for the rapid identification of the SERS spectral features of blood serum and its filtrate fractions from both healthy individuals and those with breast cancer, aiding in disease diagnosis.

Tackling antimicrobial resistance in primary care facilities across Pakistan: Current challenges and implications for the future.

Antibiotics are gradually becoming less effective against bacteria worldwide, and this issue is of particular concern in economically-developing nations like Pakistan. We undertook a scoping review in order to review the literature on antimicrobial use, prescribing, dispensing and the challenges associated with antimicrobial resistance in primary care (PC) settings in Pakistan. Furthermore, this review aims to identify potential solutions to promote appropriate use of antimicrobials in Pakistan. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) checklist, a comprehensive scoping review was conducted to review the literature of antimicrobials used, prescribed and dispensed in PC settings in Pakistan. Google Scholar and Pub-Med were searched for the period 2000-2023. Papers were analyzed on the basis of eligibility i.e., included antimicrobial use, prescribing and dispensing practices by general population at homes, by prescribers in outpatient departments of hospitals and by pharmacists/dispensers in community pharmacies, respectively. Two researchers analyzed the articles thoroughly and disagreements were resolved through discussion with a third reviewer. Both quantitative and qualitative research studies were eligible for inclusion. Additionally, the selected papers were grouped into different themes. We identified 4070 papers out of which 46 studies satisfied our eligibility criteria. The findings revealed limited understanding of antimicrobial resistance (AMR) by physicians and community pharmacists along with inappropriate practices in prescribing and dispensing antibiotics. Moreover, a notable prevalence of self-medication with antibiotics was observed among the general population, underscoring a lack of awareness and knowledge concerning proper antibiotic usage. Given the clinical and public health implications of AMR, Pakistan must prioritize its policies in PC settings. Healthcare professionals (HCPs) need to reduce inappropriate antibiotic prescribing and dispensing, improve their understanding of the AWaRe (access, watch and reserve antibiotics) classification and guidance, monitor current usage and resistance trends, as well as implement antimicrobial stewardship (ASP) activities starting in targeted locations.

Toxicity and Impact of Silica Nanoparticles on the Configuration of Gut Microbiota in Immunodeficient Mice.

Nanoparticles (NPs), having exceptional physicochemical and electrical characteristics with lower toxicity, have evolved as dynamic drug delivery carriers in living organisms. Potentially, the intragastric gavage of silica nanoparticles (SiNPs) affects gut microbiota profiles in immunodeficient mice. In this study, the impact of SiNPs of variable size and dosage was investigated in cyclophosphamide (Cy)-induced immunodeficient mice, specifically on their immune functions and gut microbiota, through physicochemical and metagenomic analysis. SiNPs of different sizes and doses were gavaged to Cy-induced immunodeficient mice for 12 days at an interval of 24 h to investigate their effects on immunological functions and the gut microbiome of mice. Our results showed that SiNPs had no significant toxicological effects on the cellular and hematological activities of immunodeficient mice. Furthermore, after the administration of different levels of SiNPs, no immune dysfunction was found in the immunosuppressed mice groups. However, gut-microbial studies and comparisons of characteristic bacterial diversity and compositions demonstrated that SiNPs significantly affect the abundance of different bacterial communities. LEfSe analysis revealed that SiNPs significantly increased the abundance of Lactobacillus, Sphingomonas, Sutterella, Akkermansia, and Prevotella, and potentially reduced Ruminococcus and Allobaculum. Thus, SiNPs significantly regulate and modify the configuration of the gut microbiota in immunodeficient mice. These dynamic variations in the intestinal bacterial community, abundance, and diversity provide new insight into the regulation and administration of silica-based NPs. This would be helpful for the further demonstration of the mechanism of action and prediction of the potential effects of SiNPs.

High level of lactate dehydrogenase and ischaemia-reperfusion injury regulate the multiple organ dysfunction in patients with COVID-19.

BACKGROUND: Multiple organ damage has been observed in patients with COVID-19, but the exact pathway is not known. Vital organs of the human body may get affected after replication of SARS-CoV-2, including the lungs, heart, kidneys, liver and brain. It triggers severe inflammation and impairs the function of two or more organ systems. Ischaemia-reperfusion (IR) injury is a phenomenon that can have disastrous effects on the human body. METHODS: In this study, we analysed the laboratory data of 7052 hospitalised patients with COVID-19 including lactate dehydrogenase (LDH). A total of 66.4% patients were men and 33.6% were women, which indicated gender difference as a prominent factor to be considered. RESULTS: Our data showed high levels of inflammation and elevated markers of tissue injury from multiple organs C reactive protein, white blood cell count, alanine transaminase, aspartate aminotransferase and LDH. The number of red blood cells, haemoglobin concentration and haematocrit were lower than normal which indicated a reduction in oxygen supply and anaemia. CONCLUSION: On the basis of these results, we proposed a model linking IR injury to multiple organ damage by SARS-CoV-2. COVID-19 may cause a reduction in oxygen towards an organ, which leads to IR injury.

Antibiotic Utilization Patterns for Different Wound Types among Surgical Patients: Findings and Implications.

Antimicrobial prophylaxis is effective in reducing the rate of surgical site infections (SSIs) post-operatively. However, there are concerns with the extent of prophylaxis post-operatively, especially in low- and middle-income countries (LMICs). This increases antimicrobial resistance (AMR), which is a key issue in Pakistan. Consequently, we conducted an observational cross-sectional study on 583 patients undergoing surgery at a leading teaching hospital in Pakistan with respect to the choice, time and duration of antimicrobials to prevent SSIs. The identified variables included post-operative prophylactic antimicrobials given to all patients for all surgical procedures. In addition, cephalosporins were frequently used for all surgical procedures, and among these, the use of third-generation cephalosporins was common. The duration of post-operative prophylaxis was 3-4 days, appreciably longer than the suggestions of the guidelines, with most patients prescribed antimicrobials until discharge. The inappropriate choice of antimicrobials combined with prolonged post-operative antibiotic administration need to be addressed. This includes appropriate interventions, such as antimicrobial stewardship programs, which have been successful in other LMICs to improve antibiotic utilization associated with SSIs and to reduce AMR.

Structural and Phylogenetic Analysis of CXCR4 Protein Reveals New Insights into Its Role in Emerging and Re-Emerging Diseases in Mammals.

Chemokine receptor type 4 (CXCR4) is a G protein-coupled receptor that plays an essential role in immune system function and disease processes. Our study aims to conduct a comparative structural and phylogenetic analysis of the CXCR4 protein to gain insights into its role in emerging and re-emerging diseases that impact the health of mammals. In this study, we analyzed the evolution of CXCR4 genes across a wide range of mammalian species. The phylogenetic study showed species-specific evolutionary patterns. Our analysis revealed novel insights into the evolutionary history of CXCR4, including genetic changes that may have led to functional differences in the protein. This study revealed that the structural homologous human proteins and mammalian CXCR4 shared many characteristics. We also examined the three-dimensional structure of CXCR4 and its interactions with other molecules in the cell. Our findings provide new insights into the genomic landscape of CXCR4 in the context of emerging and re-emerging diseases, which could inform the development of more effective treatments or prevention strategies. Overall, our study sheds light on the vital role of CXCR4 in mammalian health and disease, highlighting its potential as a therapeutic target for various diseases impacting human and animal health. These findings provided insight into the study of human immunological disorders by indicating that Chemokines may have activities identical to or similar to those in humans and several mammalian species.

Effects of thiram exposure on liver metabolism of chickens.

Pesticides are widely used to control crop diseases, which have made an important contribution to the increase of global crop production. However, a considerable part of pesticides may remain in plants, posing a huge threat to animal safety. Thiram is a common pesticide and has been proven that its residues in the feed can affect the growth performance, bone formation, and intestinal health of chickens. However, there are few studies on the liver metabolism of chickens exposed to thiram. Here, the present study was conducted to investigate the effect of thiram exposure on liver metabolism of chickens. Metabolomics analysis shows that 62 metabolites were down-regulated (ginsenoside F5, arbekacin, coproporphyrinogen III, 3-keto Fusidic acid, marmesin, isofumonisin B1, 3-Hydroxyquinine, melleolide B, naphazoline, marmesin, dibenzyl ether, etc.) and 35 metabolites were up-regulated (tetrabromodiphenyl ethers, deoxycholic acid glycine conjugate, L-Palmitoylcarnitine, austalide K, hericene B, pentadecanoylcarnitine, glyceryl palmitostearate, quinestrol, 7-Ketocholesterol, tetrabromodiphenyl ethers, etc.) in thiram-induced chickens, mainly involved in the metabolic pathways including glycosylphosphatidylinositol (GPI)-anchor biosynthesis, porphyrin and chlorophyll metabolism, glycerophospholipid metabolism, primary bile acid biosynthesis and steroid hormone biosynthesis. Taken together, this research showed that thiram exposure significantly altered hepatic metabolism in chickens. Moreover, this study also provided a basis for regulating the use and disposal of thiram to ensure environmental quality and poultry health.

Stability analysis for a class of implicit fractional differential equations involving Atangana-Baleanu fractional derivative.

Some fundamental conditions and hypotheses are established to ensure the existence, uniqueness, and stability to a class of implicit boundary value problems (BVPs) with Atangana-Baleanu-Caputo type derivative and integral. The required results are established by utilizing the Banach contraction mapping principle and fixed point theorem of Krasnoselskii. In addition, various types of stability results including Hyers-Ulam, generalized Hyers-Ulam, Hyers-Ulam-Rassias, and generalized Hyers-Ulam-Rassias stability are formulated for the problem under consideration. Pertinent examples are given to justify the results we obtain.

The interplay between the immune system and SARS-CoV-2 in COVID-19 patients.

Millions of people across the globe have been affected by coronavirus disease 2019 (COVID-19), which began in Wuhan, China, and is caused by SARS-CoV-2. COVID-19 has a variety of clinical characteristics and triggers immune responses required for the elimination of the viral agent. Currently, no effective treatment options are available for targeting SARS-CoV-2 infection. Repurposing of drugs such as chloroquine, thalidomide, and leflunomide alongside convalescent plasma is being employed as a therapeutic strategy. Clinical studies have shown that both asymptomatic and symptomatic patients can have an extremely active immune response that is largely attributable to immune system modulations. This includes cytokine storm syndrome (CSS), which affects the adaptive immune system, leading to exhaustion of natural killer (NK) cells and thrombocytopenia in some cases. This review examines the interaction of SARS-CoV-2 with the host immune system and the potential for the development of appropriate immunotherapy for the treatment of COVID-19.

Estrogen shields women from COVID-19 complications by reducing ER stress.

Estrogen hormone acts as a potential key player in providing immunity against certain viral infection. It is found to be associated in providing immunity against acute lungs inflammation and influenza virus by modulating cytokines storm and mediating adaptive immune alterations respectively. Women are less affected by SARS-CoV-2 infection because of the possible influence of estrogen hormone as compared to men. We hypothesized that SARS-CoV-2 causes stress in endoplasmic reticulum (ER) which in turn aggravates the infection, estrogen hormone might play key role in decreasing ER stress by activating estrogen mediated signaling pathways, results in unfolded protein response (UPR). Estrogen governs degradation of phosphotidylinositol 4,5-bisphosphate (PIP2) into diacylglycerol (DAG) and inositol triphosphate (IP3) with the help of phospholipase C. IP3 start in-fluxing Ca+2 ions that helps in UPR activation. To support our hypothesis, we analyzed the data of 162,392 COVID-19 patients to determine the relation of this disease with gender. We observed that 26% of women and 74% of men were affected by SARS-CoV-2. It indicated that women are less affected because of the possible influence of estrogen hormone in women.