Carveol mitigates the development of the morphine anti-nociceptive tolerance, physical dependence, and conditioned place preference in mice.

Emergence of analgesic tolerance and dependence to morphine is frequently the limiting factor in the use of this agent in the management of pain. Hence, this study aimed to investigate the beneficial effects of the natural compound carveol (CV) against morphine antinociceptive tolerance, dependence and conditioned place preference (CPP) in mice. Behavioural paradigms included hot plate and tail-flick (for tolerance), observation of withdrawal signs (for dependence) while biochemical tests involved the assays for mRNA expression, nitrite levels, antioxidants, and immunohistochemistry studies. Behavioural tests indicated that treatment with CV significantly attenuated the morphine analgesic tolerance, physical dependence and CPP in mice. It was observed during biochemical analysis that CV-treated animals exhibited reduced mRNA expression of inducible nitric oxide synthase (iNOS) and NR2B (an NMDA subtype). In addition, decreased levels of nitrite were observed in mouse hippocampus following CV treatment than morphine administration only. Further, CV enhanced the neuronal innate antioxidants including Glutathione-S-Transferase (GST), glutathione (GSH) and catalase (CAT), while curtailed lipid peroxidase (LPO) levels in mice brain tissues. Moreover, CV exerted significant anti-inflammatory effects as evidenced by reduced expression of TNF-α and p-NF-κB in these animals than with morphine treatment only. Together, anti-inflammatory and antioxidant effects might confer needed neuro-protection following morphine administration. These observations warrant further investigations of the beneficial role of CV as a novel agent in overcoming the development of tolerance and physical dependence following morphine use.

Updated review on analysis of long non-coding RNAs as emerging diagnostic and therapeutic targets in prostate cancers.

Despite advancements, prostate cancers (PCa) pose a significant global health challenge due to delayed diagnosis and therapeutic resistance. This review delves into the complex landscape of prostate cancer, with a focus on long-noncoding RNAs (lncRNAs). Also explores the influence of aberrant lncRNAs expression in progressive PCa stages, impacting traits like proliferation, invasion, metastasis and therapeutic resistance. The study elucidates how lncRNAs modulate crucial molecular effectors, including transcription factors and microRNAs, affecting signaling pathways such as androgen receptor signaling. Besides, this manuscript sheds light on novel concepts and mechanisms driving PCa progression through lncRNAs, providing a critical analysis of their impact on the disease's diverse characteristics. Besides, it discusses the potential of lncRNAs as diagnostics and therapeutic targets in PCa. Collectively, this work highlights state of art mechanistic comprehension and rigorous scientific approaches to advance our understanding of PCa and depict innovations in this evolving field of research.

Dynamics of Malaria Incidence in Khyber Pakhtunkhwa, Pakistan: Unveiling Rapid Growth Patterns and Forecasting Future Trends.

BACKGROUND: Malaria remains a formidable worldwide health challenge, with approximately half of the global population at high risk of catching the infection. This research study aimed to address the pressing public health issue of malaria's escalating prevalence in Khyber Pakhtunkhwa (KP) province, Pakistan, and endeavors to estimate the trend for the future growth of the infection. METHODS: The data were collected from the IDSRS of KP, covering a period of 5 years from 2018 to 2022. We proposed a hybrid model that integrated Prophet and TBATS methods, allowing us to efficiently capture the complications of the malaria data and improve forecasting accuracy. To ensure an inclusive assessment, we compared the prediction performance of the proposed hybrid model with other widely used time series models, such as ARIMA, ETS, and ANN. The models were developed through R-statistical software (version 4.2.2). RESULTS: For the prediction of malaria incidence, the suggested hybrid model (Prophet and TBATS) surpassed commonly used time series approaches (ARIMA, ETS, and ANN). Hybrid model assessment metrics portrayed higher accuracy and reliability with lower MAE (8913.9), RMSE (3850.2), and MAPE (0.301) values. According to our forecasts, malaria infections were predicted to spread around 99,301 by December 2023. CONCLUSIONS: We found the hybrid model (Prophet and TBATS) outperformed common time series approaches for forecasting malaria. By December 2023, KP's malaria incidence is expected to be around 99,301, making future incidence forecasts important. Policymakers will be able to use these findings to curb disease and implement efficient policies for malaria control.

Adsorption of Eosin B from Wastewater onto the Prepared Porous Anion Exchange Membrane.

This research describes the fabrication of the porous trimethylamine (TMA)-grafted anion exchange membrane (AEM) over a phase inversion process. The synthesis of the generated AEM was verified using Fourier transform infrared (FTIR) spectroscopy. The fabricated porous AEM showed 240% water uptake (WR), 1.45 mg/g ion exchange capacity (IEC), and a 9.0% linear expansion ratio (LER) at 25 °C. It exhibited a porous structure and higher thermal stability. It was utilized to remove eosin B (EB) from wastewater via the process of adsorption. The adsorption capacity of EB increased with time and the starting concentration of EB while decreasing with temperature and the AEM dosage. Adsorption isotherm investigation results showed that EB adsorption onto the porous AEM followed the Langmuir isotherm because the value of correlation coefficient (R2 = 0.992) was close to unity. Because the correlation coefficient was close to one, it was determined through adsorption kinetic experiments that the adsorption of EB on the produced porous AEM was suitable for a pseudo-second-order model. Thermodynamic study about process of EB adsorption on the porous AEM revealed that there was an exothermic (ΔH° = -16.60 kJ/mol) and spontaneous process.

Injectable Chitosan-Methoxy Polyethylene Glycol Hybrid Hydrogel Untangling the Wound Healing Behavior: In Vitro and In Vivo Evaluation.

Wound healing, particularly for difficult-to-treat wounds, presents a serious threat and may lead to complications. Currently available dressings lack mucoadhesion, safety, efficacy, and, most importantly, patient compliance. Herein, we developed a unique, simple, and inexpensive injectable chitosan-methoxy polyethylene glycol (chitosan-mPEG) hybrid hydrogel with tunable physicochemical and mechanical properties for wound healing. The detailed physicochemical and rheological characterization of the chitosan-mPEG hydrogel has revealed chemical interaction between available -NH2 groups of chitosan and -COOH groups of mPEG acid, which, to our perspective, enhanced the mechanical and wound healing properties of hybrid chitosan and mPEG hydrogel compared to solo chitosan or PEG hydrogel. By introducing mPEG, the wound healing ability of hydrogel is synergistically improved due to its antibacterial feature, together with chitosan's innate role in hemostasis and wound closure. The detailed hemostasis and wound closure potential of the chitosan-mPEG hydrogel were investigated in a rat model, which confirmed a significant acceleration in wound healing and ultimately wound closure. In conclusion, the developed chitosan-mPEG hydrogel met all the required specifications and could be developed as a promising material for hemostasis, especially wound management, and as an excellent candidate for wound healing application.

A comprehensive review on the applications of ferrite nanoparticles in the diagnosis and treatment of breast cancer.

Various conventional treatments including endocrine therapy, radiotherapy, surgery, and chemotherapy have been used for several decades to treat breast cancer; however, these therapies exhibit various life-threatening and debilitating adverse effects in patients. Additionally, combination therapies are required for prompt action as well as to prevent drug resistance toward standard breast cancer medications. Ferrite nanoparticles (NPs) are increasingly gaining momentum for their application in the diagnosis and treatment of breast cancer. Spinel ferrites are particularly used against breast cancer and have shown in vitro and in vivo better efficacy as compared to conventional cancer therapies. Magnetic resonance imaging contrast agents, magnetic particle imaging tracers, cell separation, and immune assays are some aspects related to the diagnosis of breast cancer against which different ferrite NPs have been successfully evaluated. Moreover, citrate-coated nickel ferrite, Mg/Zn ferrites, poly amidoamine dendrimers, cobalt ferrites, graphene oxide cobalt ferrites, doxorubicin functionalized cobalt ferrites, chitosan-coated zinc ferrites, PEG-coated cobalt ferrite, and copper ferrite NPs have demonstrated antiproliferative action against different breast cancer cells. Oxaliplatin-loaded polydopamine/BSA-copper ferrites, functionalized cobalt and zinc ferrites of curcumin, oxaliplatin-copper ferrite NPs, tamoxifen/diosgenin encapsulated ZnO/Mn ferrites, and fabricated core-shell fibers of doxorubicin have been developed to increase the bioavailability and anti-proliferative effect and decrease the toxicity of anticancer drugs. These ferrite NPs showed an anticancer effect at different doses in the presence or absence of an external magnetic field. The present review covers the in-depth investigations of ferrite NPs for the diagnosis and management of breast cancer.

Microbes-assisted phytoremediation of lead and petroleum hydrocarbons contaminated water by water hyacinth.

An experiment was carried out to explore the impact of petroleum hydrocarbons (PHs)-degrading microbial consortium (MC) on phytoremediation ability and growth of water hyacinth (WH) plants in water contaminated with lead (Pb) and PHs. Buckets (12-L capacity) were filled with water and WH plants, PHs (2,400 mg L-1) and Pb (10 mg L-1) in respective buckets. Plants were harvested after 30 days of transplanting and results showed that PHs and Pb substantially reduced the agronomic (up to 62%) and physiological (up to 49%) attributes of WH plants. However, the application of MC resulted in a substantial increase in growth (38%) and physiology (22%) of WH plants over uninoculated contaminated control. The WH + MC were able to accumulate 93% Pb and degrade/accumulate 72% of PHs as compared to initial concentration. Furthermore, combined use of WH plants and MC in co-contamination of PHs and Pb, reduced Pb and PHs contents in water by 74% and 68%, respectively, than that of initially applied concentration. Our findings suggest that the WH in combination with PHs-degrading MC could be a suitable nature-based water remediation technology for organic and inorganic contaminants and in future it can be used for decontamination of mix pollutants from water bodies.

Phytoremediation by aquatic macrophytes is a promising technique for the cleanup of environmental toxins from wastewater. To our knowledge, this is the first study reporting the integrated use of water hyacinth (WH) plants and a newly developed multi-trait microbial consortium for the simultaneous remediation of organic (i.e., petroleum hydrocarbons) and inorganic (i.e., lead) pollutants from the contaminated water. Findings of this study provide the basic but important information on the combined use of WH and microbes for remediation of mix pollution from water bodies.

Expression of concern: Influence of chemical composition on the amount of second phases precipitates and transformation temperatures of TiNiPdCu shape memory alloys prepared through novel powder metallurgy route.

Expression of concern for 'Influence of chemical composition on the amount of second phases precipitates and transformation temperatures of TiNiPdCu shape memory alloys prepared through novel powder metallurgy route' by Abid Hussain et al., RSC Adv., 2023, 13, 29376-29392, https://doi.org/10.1039/D3RA05513B.

Correction: Khan et al. Therapeutic Effects of Saponins for the Prevention and Treatment of Cancer by Ameliorating Inflammation and Angiogenesis and Inducing Antioxidant and Apoptotic Effects in Human Cells. Int. J. Mol. Sci. 2022, 23, 10665.

In the original publication by Khan et al [...].

Prognostic value of whole-body dynamic 18F-FDG PET/CT Patlak in diffuse large B-cell lymphoma.

Objective: This study aims to investigate the significance of interim whole-body dynamic 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) Patlak parameters for predicting the prognosis of patients with diffuse large B-cell lymphoma. To estimate the predictive value of the whole-body dynamic 18F-FDG PET/CT Patlak parameter for 2-year progression-free survival (PFS) and 2-year overall survival (OS). Methods: This study reports the findings of 67 patients with diffuse large B-cell lymphoma (DLBCL). These patients underwent interim whole-body dynamic 18F-FDG PET/CT scans from June 2021 to January 2023 at the Department of Nuclear Medicine, First Affiliated Hospital of Anhui Medical University. The predictive values of maximum standard uptake value (SUVmax), maximum of net glucose uptake rate (Kimax) and the predictive model combining Kimax and interim treatment response on the prognosis of patients was analyzed using receiver operating characteristic (ROC) curves. Kaplan-Meier survival curves and log-rank tests were used for survival analysis. Univariate and multivariate analyses were performed to screen for independent prognostic risk factors. Results: After a median follow-up of 18 months, 21 patients (31.3%) experienced disease recurrence or death. The cut-off values for the SUVmax and the Kimax were 6.1 and 0.13 µmol min-1·ml-1, respectively. Ann Arbor stage, IPI, SUVmax, Kimax and interim treatment response were associated with PFS and OS in the univariate analysis. However, only Kimax and interim treatment response were independent influences on PFS and OS in multivariate analysis. Conclusion: Interim whole-body dynamic 18F-FDG PET/CT Patlak imaging has significant prognostic value in patients with DLBCL. Among them, the interim dynamic parameter Kimax showed the best predictive value for prognosis compared with the interim SUVmax and interim treatment response. The predictive model established by Kimax and the interim treatment response allowed for the accurate stratification of the prognostic risk of DLBCL.

Influence of chemical composition on the amount of second phases precipitates and transformation temperatures of TiNiPdCu shape memory alloys prepared through novel powder metallurgy route.

The chemical composition of TiNiPdCu high temperature shape memory alloys (HTSMAs) affects their microstructure and martensitic transformations. In TiNiPdC HTSMAs, second phase precipitates were found. Extremely high densities of nanoscale precipitates of TiPdCu and Ti2Pd of particle size 0.8-4.4 µm were found to be produced by the TiNiPdCu alloys. It was found that the TiPdCu-type precipitates were favoured by the preferential migration of Cu atoms towards the heterogeneous nucleation sites, which in turn favoured the fine Ti2Pd-type precipitates. Due primarily to their high-temperature stability, these precipitates significantly strengthened the resistance against transformation-induced plasticity and creep deformation, especially at high loads and high temperatures. High concentrations of these nanoscaled precipitates led to a significant rise in transformation temperatures by 12% and a small decrease in thermal hysteresis by 30%. It was anticipated that the current research findings will have a significant positive impact on the creation of HTSMAs that maintain their benefits of simplicity of manufacture. The HTSMAs developed in current research are beneficial for high temperature sensors and actuators at optimum cost.

The prevalence of prostate cancer in Pakistan: A systematic review and meta-analysis.

Background: Prostate cancer is a significant public health issue, ranking as the second most common cancer and the fifth leading cause of cancer-related deaths in men. In Pakistan, the prevalence of prostate cancer varies significantly across published articles. This study aimed to determine the pooled prevalence of prostate cancer and its associated risk factors in Pakistan. Methods: MEDLINE (via PubMed), Web of Science, Google Scholar, and local databases were searched from inception until March 2023, using key search terms related to the prevalence of prostate cancer. We considered a random-effects meta-analysis to derive the pooled prevalence and relative risks with 95% CIs. Two investigators independently screened articles and performed data extraction and risk of bias analysis. We also conducted meta-regression analysis and stratification to investigate heterogeneity. This study protocol was registered at PROSPERO, number CRD42022376061. Results: Our meta-analysis incorporated 11 articles with a total sample size of 184,384. The overall pooled prevalence of prostate cancer was 5.20% (95% CI: 3.72-6.90%), with substantial heterogeneity among estimates (I2 = 98.5%). The 95% prediction interval of prostate cancer was ranged from 1.74%-10.35%. Subgroup meta-analysis revealed that the highest pooled prevalence of prostate cancer was in Khyber Pakhtunkhwa (8.29%; 95% CI: 6.13-10.74%, n = 1), followed by Punjab (8.09%; 95% CI:7.36-8.86%, n = 3), while the lowest was found in Sindh (3.30%; 95% CI: 2.37-4.38%, n = 5). From 2000 to 2010 to 2011-2023, the prevalence of prostate cancer increased significantly from 3.88% (95% CI: 2.72-5.23%) to 5.80% (95% CI: 3.76-8.24%). Conclusions: Our meta-analysis provides essential insights into the prevalence of prostate cancer in Pakistan, highlighting the need for continued research and interventions to address this pressing health issue.

Stem cells-derived exosomes alleviate neurodegeneration and Alzheimer's pathogenesis by ameliorating neuroinflamation, and regulating the associated molecular pathways.

Amyloid beta (Aß) aggregation and tau hyper phosphorylation (p-tau) are key molecular factors in Alzheimer's disease (AD). The abnormal formation and accumulation of Aß and p-tau lead to the formation of amyloid plaques and neurofibrillary tangles (NFTs) which ultimately leads to neuroinflammation and neurodegeneration. ß- and γ-secretases produce Aß peptides via the amyloidogenic pathway, and several kinases are involved in tau phosphorylation. Exosomes, a recently developed method of intercellular communication, derived from neuronal stem cells (NSC-exos), are intriguing therapeutic options for AD. Exosomes have ability to cross the BBB hence highly recommended for brain related diseases and disorders. In the current study, we examined how NSC-exos could protect human neuroblastoma cells SH-SY5Y (ATCC CRL-2266). NSC-exos were derived from Human neural stem cells (ATCC-BYS012) by ultracentrifugation and the therapeutic effects of the NSC-exos were then investigated in vitro. NSC-exos controlled the associated molecular processes to drastically lower Aß and p-tau. A dose dependent reduction in ß- and γ-secretase, acetylcholinesterase, GSK3ß, CDK5, and activated α-secretase activities was also seen. We further showed that BACE1, PSEN1, CDK5, and GSK-3ß mRNA expression was suppressed and downregulated, while ADAM10 mRNA was increased. NSC- Exos downregulate NF-B/ERK/JNK-related signaling pathways in activated glial cells HMC3 (ATCC-CRL-3304) and reduce inflammatory mediators such iNOS, IL-1ß, TNF-α, and IL-6, which are associated with neuronal inflammation. The NSC-exos therapy ameliorated the neurodegeneration of human neuroblastoma cells SH-SY5Y by enhancing viability. Overall, these findings support that exosomes produced from stem cells can be a neuro-protective therapy to alleviate AD pathology.

Synthesis and characterization of Hyaluronic Acid (HA) modified polymeric composite for effective treatment of wound healing by transdermal drug delivery system (TDDS).

The present study aimed to fabricate a novel polymeric spongy composite to enhance skin regeneration composed of Nystatin (antifungal agent) and Silver Nanoparticles (AgNps). Different formulations (F1-F8) were developed & characterized by using various analytical techniques. AgNps synthesized by chemical reduction method showed spherical morphology 2 µm in size showed by SEM and XRD. A fine porous structure of gel embedded with AgNps having an amorphous structure with 10 % crystallinity due to AgNps was found. IR spectra revealed no chemical interaction between polymers and Nystatin. An increase in thermal stability of formulation was observed till 700 â„ƒ analyzed by Differential Scanning Calorimetry. Cytotoxic analysis on L929 mouse skin fibroblast cells showed a decrease in cell viability as Ag concentration increased (inactivating Fibroblast and keratinocytes) while 10 mg composition was found safest concentration (94%). Optimized formulation (F2) presented in-vitro drug release up to 90.59% ± 0.76 at pH 7.4, swelling studies (87.5% ± 0.57), water retention (26.60 ± 0.34), pH (5.31 ± 0.03). In the animal burn model, the group that received CHG/Ag/Nystatin healed the wound significantly (p < 0.05). These results suggested that optimized carrier can be used for other anti-fungal drugs facilitating the early healing of the wound.

Chemical Characterization and Ameliorating Effect of Centratherum anthelminticum Extract against Polycystic Ovary Syndrome in Wistar Rats.

Polycystic ovary syndrome (PCOS) in females is an endocrine pathological condition of reproductive age which is usually caused by insulin resistance, hyperlipidemia, and oxidative stress. This research was aimed at evaluating the therapeutic effect of the Centratherum anthelminticum seed extract (CA) against PCOS in rodents as it is traditionally used to treat diabetes, inflammation, and gynecological problems. The CA was chemically characterized by high-performance liquid chromatography-diode array detection (HPLC-DAD). For the induction of PCOS, a high-fat diet (HFD) was given to all female Wistar rats for nine weeks except the normal control group, which was given a normal chow diet. Estradiol valerate was given to all rats except normal control. After the induction of PCOS, oral metformin (300 mg/kg) was given to the standard group, while CA was orally administered to diseased rats at 250, 500, and 750 mg/kg/day for 28 days. HPLC-DAD analysis revealed that kaempferol-3-pcoumaroylglucoside was present in the highest amount (146.8 ± 1.8 mg/g) of the extract followed by ferulic acid and malvidin-3-(6-caffeoyl)-glucoside. The in vivo results revealed a marked reduction in cholesterol and triglyceride levels in CA treatment groups. A significant rise was observed in progesterone and follicle stimulating hormone with a decrease in luteinizing hormone in the treatment groups as compared to disease control, which indicated normalization of the estrus cycle. The decrease in insulin resistance was characterized by low serum insulin levels in treatment groups. Treatment with CA also reduced inflammatory markers, such as IL-6 and NF-κB in PCOS rats. NrF2 and oxidative stress markers such as catalase, superoxide dismutase, malondialdehyde, and reduced glutathione were also improved by CA in the ovary of diseased rats. Histopathological examination showed the different developmental stages of normal follicles in CA-treated diseased rats which were indicative of a normal fertile estrous cycle. Overall, the results confirmed the efficacy of CA against PCOS in treating estradiol-HFD-induced PCOS due to its antidiabetic, anti-inflammatory, antihyperlipidemic, and antioxidant properties.

Molecular mechanisms of morphine tolerance and dependence; novel insights and future perspectives.

Drug addiction is a devastating condition that poses a serious burden on the society. The use of some drugs like morphine for their tremendous analgesic properties is also accompanied with developing tolerance, dependence and the withdrawal symptoms. These symptoms are frequently severe enough to reinforce the person in recovery to start over the use of drug again and hinder the clinical use of drugs like morphine for chronic pain. Research into opioid receptors and related molecular pathways has seen resurgence in the wake of the growing opioid epidemic. The current study provides a comprehensive scientific exploration of the molecular mechanisms and underlying signalling in morphine tolerance and dependence. It also critically evaluates current therapeutic approaches, shedding light on their efficacy and limitations, and future prospects. The graphical abstract depicts an overview of the pathways involved in the emergence of morphine-related tolerance and dependence including NMDA, Nitric oxide, and PPAR, as well as behavioural sensitization along with present and future innovative treatment strategies including stem cell therapy that have been discussed in the current manuscript.

Genetic causes of inherited retinal diseases among Israeli Jews of Ethiopian ancestry.

Purpose: This study sought to describe the phenotype frequency and genetic basis of inherited retinal diseases (IRDs) among a nationwide cohort of Israeli Jewish patients of Ethiopian ancestry. Methods: Patients' data-including demographic, clinical, and genetic information-were obtained through members of the Israeli Inherited Retinal Disease Consortium (IIRDC). Genetic analysis was performed by either Sanger sequencing for founder mutations or next-generation sequencing (targeted next-generation sequencing or whole-exome sequencing). Results: Forty-two patients (58% female) from 36 families were included, and their ages ranged from one year to 82 years. Their most common phenotypes were Stargardt disease (36%) and nonsyndromic retinitis pigmentosa (33%), while their most common mode of inheritance was autosomal recessive inheritance. Genetic diagnoses were ascertained for 72% of genetically analyzed patients. The most frequent gene involved was ABCA4. Overall, 16 distinct IRD mutations were identified, nine of which are novel. One of them, ABCA4-c.6077delT, is likely a founder mutation among the studied population. Conclusions: This study is the first to describe IRDs' phenotypic and molecular characteristics in the Ethiopian Jewish community. Most of the identified variants are rare. Our findings can help caregivers with clinical and molecular diagnosis and, we hope, enable adequate therapy in the near future.

Microneedle array facilitates hepatic sinusoid construction in a large-scale liver-acinus-chip microsystem.

Hepatic sinusoids play a key role in maintaining high activities of liver cells in the hepatic acinus. However, the construction of hepatic sinusoids has always been a challenge for liver chips, especially for large-scale liver microsystems. Herein, we report an approach for the construction of hepatic sinusoids. In this approach, hepatic sinusoids are formed by demolding a self-developed microneedle array from a photocurable cell-loaded matrix in a large-scale liver-acinus-chip microsystem with a designed dual blood supply. Primary sinusoids formed by demolded microneedles and spontaneously self-organized secondary sinusoids can be clearly observed. Benefiting from significantly enhanced interstitial flows by formed hepatic sinusoids, cell viability is witnessed to be considerably high, liver microstructure formation occurs, and hepatocyte metabolism is enhanced. In addition, this study preliminarily demonstrates the effects of the resulting oxygen and glucose gradients on hepatocyte functions and the application of the chip in drug testing. This work paves the way for the biofabrication of fully functionalized large-scale liver bioreactors.

Adverse health effects and mechanisms of microplastics on female reproductive system: a descriptive review.

Microplastics (MPs), with a diameter of less than 5 mm, include polymers such as polystyrene, polypropylene, and polyethylene. The MPs occur in different morphologies including fragments, beads, fibers, and films that are swallowed by fresh water and land-based animals and enter their food chain, where they produce hazardous effects such as uterine toxicity, infertility, and neurotoxicity. The aim of this review is to explore the effects of polystyrene MPs (PS-MPs) on the female reproductive system and understand the mechanisms by which they produce reproductive toxicity. Several studies suggested that the exposure to PS-MPs increased the probability of larger ovaries with fewer follicles, decreased the number of embryos produced, and decreased the number of pregnancies in female mice. It also changed sex hormone levels and caused oxidative stress, which could have an impact on fertility and reproduction. Exposure to PS-MPs caused the death of granulosa cells through apoptosis and pyroptosis via activation of the NLRP3/caspase pathway and disruption of the Wnt-signaling pathway. Activation of TL4/NOX2 caused the uterine fibrosis resulting in endometrium thinning. The PS-MPs had a negative impact on ovarian capacity, oocyte maturation, and oocyte quality. Furthermore, the PS-MPs disrupted the hypothalamus-pituitary-gonadal axis in marine animals, resulting in a decrease in hatching rate and offspring body size, causing trans-generational effects. It also reduced fecundity and produced germ-line apoptosis. The main focus of this review was to explore the different mechanisms and pathways through which PS-MPs adversely impact the female reproductive system.

Reprogramming tumor-associated macrophages as a unique approach to target tumor immunotherapy.

In the last ten years, it has become increasingly clear that tumor-infiltrating myeloid cells drive not just carcinogenesis via cancer-related inflammatory processes, but also tumor development, invasion, and metastasis. Tumor-associated macrophages (TAMs) in particular are the most common kind of leucocyte in many malignancies and play a crucial role in establishing a favorable microenvironment for tumor cells. Tumor-associated macrophage (TAM) is vital as the primary immune cell subset in the tumor microenvironment (TME).In order to proliferate and spread to new locations, tumors need to be able to hide from the immune system by creating an immune-suppressive environment. Because of the existence of pro-tumoral TAMs, conventional therapies like chemotherapy and radiotherapy often fail to restrain cancer growth. These cells are also to blame for the failure of innovative immunotherapies premised on immune-checkpoint suppression. Understanding the series of metabolic changes and functional plasticity experienced by TAMs in the complex TME will help to use TAMs as a target for tumor immunotherapy and develop more effective tumor treatment strategies. This review summarizes the latest research on the TAMs functional status, metabolic changes and focuses on the targeted therapy in solid tumors.