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1.
Pathol Res Pract ; 257: 155285, 2024 Apr 05.
Article En | MEDLINE | ID: mdl-38653089

Glioblastoma, a highly lethal form of brain cancer, is characterized by its aggressive growth and resistance to conventional treatments, often resulting in limited survival. The response to therapy is notably influenced by various patient-specific genetic factors, underscoring the disease's complexity. Despite the utilization of diverse treatment modalities such as surgery, radiation, and chemotherapy, many patients experience local relapse, emphasizing the critical need for improved therapeutic strategies to effectively target these formidable tumors. Recent years have witnessed a surge in interest in natural products derived from plants, particularly alkaloids, for their potential anticancer effects. Alkaloids have shown promise in cancer chemotherapy by selectively targeting crucial signaling pathways implicated in tumor progression and survival. Specifically, they modulate the NF-κB and MAPK pathways, resulting in reduced tumor growth and altered gene expression across various cancer types. Additionally, alkaloids exhibit the capacity to induce cell cycle arrest, further impeding tumor proliferation in several malignancies. This review aims to delineate recent advances in understanding the pathology of glioblastoma multiforme (GBM) and to explore the potential therapeutic implications of alkaloids in managing this deadly disease. By segregating discussions on GBM pathology from those on alkaloid-based therapies, we provide a structured overview of the current challenges in GBM treatment and the promising opportunities presented by alkaloid-based interventions. Furthermore, we briefly discuss potential future directions in GBM research and therapy beyond alkaloids, including emerging treatment modalities or areas of investigation that hold promise for improving patient outcomes. In conclusion, our efforts offer hope for enhanced outcomes and improved quality of life for GBM patients through alkaloid-based therapies. By integrating insights from pathology and therapeutic perspectives, we underscore the significance of a comprehensive approach in addressing this devastating disease.

2.
Toxicon ; 242: 107707, 2024 May 06.
Article En | MEDLINE | ID: mdl-38579983

This research presents the synthesis and characterization of Cu-doped Fe3O4 (Cu-Fe3O4) nanoparticles as a magnetically recoverable and reusable detoxifying agent for the efficient and long-lasting neutralization of bacterial toxins. The nanoparticles were synthesized using the combustion synthesis method and characterized through SEM, XRD, BET, TGA, and VSM techniques. The detoxification potential of Cu-Fe3O4 was compared with traditional formaldehyde (FA) in detoxifying epsilon toxin (ETx) from Clostridium perfringens Type D, the causative agent of enterotoxemia in ruminants. In vivo residual toxicity tests revealed that Cu-Fe3O4 could detoxify ETx at a concentration of 2.0 mg mL-1 within 4 days at room temperature (RT) and 2 days at 37 °C, outperforming FA (12 and 6 days at RT and 37 °C, respectively). Characterization studies using dynamic light scattering (DLS) and circular dichroism (CD) highlighted lower conformational changes in Cu-Fe3O4-detoxified ETx compared to FA-detoxified ETx. Moreover, Cu-Fe3O4-detoxified ETx exhibited exceptional storage stability at 4 °C and RT for 6 months, maintaining an irreversible structure with no residual toxicity. The particles demonstrated remarkable reusability, with the ability to undergo five continuous detoxification batches. This study provides valuable insights into the development of an efficient and safe detoxifying agent, enabling the production of toxoids with a native-like structure. The magnetically recoverable and reusable nature of Cu-Fe3O4 nanoparticles offers practical advantages for easy recovery and reuse in detoxification reactions.


Bacterial Toxins , Copper , Formaldehyde , Formaldehyde/chemistry , Copper/chemistry , Animals , Bacterial Toxins/chemistry , Bacterial Toxins/toxicity , Clostridium perfringens , Magnetite Nanoparticles/chemistry
3.
Glob Med Genet ; 11(1): 69-75, 2024 Jan.
Article En | MEDLINE | ID: mdl-38440355

Background In addition to its multifaceted physiological functions, vitamin D is recognized for its protective role against cancer. To manifest its effects, vitamin D engages with the vitamin D receptor ( VDR ) gene responsible for its encoding. Investigations have unveiled that polymorphisms within the VDR gene exert influence over the expression and/or functionality of the VDR protein. Notably, certain VDR gene polymorphisms have emerged as particularly pertinent in the context of tumorigenesis, including Fok1 (rs2228570), Bsm1 (rs1544410), Taq1 (rs771236), and Apa1 (rs7975232). This study aims to scrutinize the correlation between the Bsm1 and Apa1 polymorphisms and the susceptibility to breast cancer development. Materials and Methods In this study, 50 patients suffering from breast cancer with less than 6 months breast cancer diagnosis and 50 healthy control individuals have been chosen. Restriction fragment length polymorphism polymerase chain reaction was used to determine the genotype of polymorphisms. Results The results of the statistical analysis showed that among the studied polymorphisms, there was no correlation with the development of breast cancer. Conclusion Studies on various cancers have produced inconsistent results regarding vitamin D's role in the development and progression of cancer. Therefore, further research is necessary to determine vitamin D's role in cancer development and progression.

4.
Article En | MEDLINE | ID: mdl-38279763

Glioblastoma multiforme (GBM) is a highly invasive brain malignancy originating from astrocytes, accounting for approximately 30% of central nervous system malignancies. Despite advancements in therapeutic strategies including surgery, chemotherapy, and radiopharmaceutical drugs, the prognosis for GBM patients remains dismal. The aggressive nature of GBM necessitates the identification of molecular targets and the exploration of effective treatments to inhibit its proliferation. The Notch signaling pathway, which plays a critical role in cellular homeostasis, becomes deregulated in GBM, leading to increased expression of pathway target genes such as MYC, Hes1, and Hey1, thereby promoting cellular proliferation and differentiation. Recent research has highlighted the regulatory role of non-coding RNAs (ncRNAs) in modulating Notch signaling by targeting critical mRNA expression at the post-transcriptional or transcriptional levels. Specifically, various types of ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been shown to control multiple target genes and significantly contribute to the carcinogenesis of GBM. Furthermore, these ncRNAs hold promise as prognostic and predictive markers for GBM. This review aims to summarize the latest studies investigating the regulatory effects of ncRNAs on the Notch signaling pathway in GBM.

5.
Comput Biol Med ; 166: 107518, 2023 Sep 27.
Article En | MEDLINE | ID: mdl-37806058

BACKGROUND: Histone deacetylase 2 (HDAC2), belonging to the class I HDAC family, holds significant therapeutic potential as a crucial target for diverse cancer types. As key players in the realm of epigenetic regulatory enzymes, histone deacetylases (HDACs) are intricately involved in the onset and progression of cancer. Consequently, pursuing isoform-specific inhibitors targeting histone deacetylases (HDACs) has garnered substantial interest in both biological and medical circles. The objective of the present investigation was to employ a drug repurposing approach to discover novel and potent HDAC2 inhibitors. MATERIALS AND METHODS: In this study, our protocol is presented on virtual screening to identify novel potential HDAC2 inhibitors through 3D-QSAR, molecular docking, pharmacophore modeling, and molecular dynamics (MD) simulation. Afterward, In-vitro assays were employed to evaluate the cytotoxicity, apoptosis, and migration of HCT-116 cell lines under treatment of hit compound and valproic acid as a control inhibitor. The expression levels of HDAC2, TP53, BCL2, and BAX were evaluated by QRT-PCR. RESULTS: RMSD, RMSF, H-bond, and DSSP analysis results confirmed that among bioinformatically selected compounds, lansoprazole exhibited the highest HDAC2 inhibitory potential. Experimental validation revealed that lansoprazole displayed significant antiproliferative activity. The determined IC50 value was 400 ± 2.36 µM. Furthermore, the apoptotic cells ratio concentration-dependently increased under Lansoprazole treatment. Results of the Scratch assay indicated that lansoprazole led to decreasing the migration of CRC cells. Finally, under Lansoprazole treatment the expression level of BCL2 and HDAC2 decreased and BAX and TP53 increased. CONCLUSION: Taking together the results of the current study indicated that Lansoprazole as a novel HDAC2 inhibitor, could be used as a potential therapeutic agent for the treatment of CRC. Although, further experimental studies should be performed before using this compound in the clinic.

6.
Stem Cell Rev Rep ; 19(8): 2576-2596, 2023 11.
Article En | MEDLINE | ID: mdl-37723364

Rapid advancement in genome editing technologies has provided new promises for treating neoplasia, cardiovascular, neurodegenerative, and monogenic disorders. Recently, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has emerged as a powerful gene editing tool offering advantages, including high editing efficiency and low cost over the conventional approaches. Human pluripotent stem cells (hPSCs), with their great proliferation and differentiation potential into different cell types, have been exploited in stem cell-based therapy. The potential of hPSCs and the capabilities of CRISPR/Cas9 genome editing has been paradigm-shifting in medical genetics for over two decades. Since hPSCs are categorized as hard-to-transfect cells, there is a critical demand to develop an appropriate and effective approach for CRISPR/Cas9 delivery into these cells. This review focuses on various strategies for CRISPR/Cas9 delivery in stem cells.


CRISPR-Cas Systems , Pluripotent Stem Cells , Humans , CRISPR-Cas Systems/genetics , Gene Editing , Cell Differentiation , Stem Cell Transplantation
7.
Med Oncol ; 40(11): 308, 2023 Sep 27.
Article En | MEDLINE | ID: mdl-37755616

Cancer is one of the deadliest and most heterogeneous diseases. Cancers often develop drug resistance, which can lead to treatment failure or recurrence. Accordingly, anticancer compounds are essential for chemotherapy-resistant cancer cells. Phenolic compounds are of interest in the development of cancer drugs due to their medicinal properties and ability to target different molecular pathways. Gallic acid (GA), as one of the main components of phenol, which is abundantly present in plant compounds such as walnut, sumac, grapes, tea leaves, oak bark, and other plant compounds, has antitumor properties. GA can prevent cancer progression, cell invasion, and metastasis by targeting molecular pathways and is an effective complement to chemotherapy drugs and combating multidrug resistance (MDR). In this review, we discuss various mechanisms related to cancer, the therapeutic potential of GA, the antitumor properties of GA in various cancers, and the targeted delivery of GA with nanocarriers.


Antineoplastic Agents , Neoplasms , Humans , Gallic Acid/pharmacology , Gallic Acid/therapeutic use , Drug Resistance, Neoplasm , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Signal Transduction , Neoplasms/drug therapy
8.
Ther Deliv ; 14(4): 311-329, 2023 04.
Article En | MEDLINE | ID: mdl-37403985

This review explores the potential of photonic nanoparticles for cancer theranostics. Photonic nanoparticles offer unique properties and photonics capabilities that make them promising materials for cancer treatment, particularly in the presence of near-infrared light. However, the size of the particles is crucial to their absorption of near-infrared light and therapeutic potential. The limitations and challenges associated with the clinical use of photonic nanoparticles, such as toxicity, immune system clearance, and targeted delivery to the tumor are also discussed. Researchers are investigating strategies such as surface modification, biodegradable nanoparticles, and targeting strategies to improve biocompatibility and accumulation in the tumor. Ongoing research suggests that photonic nanoparticles have potential for cancer theranostics, further investigation and development are necessary for clinical use.


Tiny particles called 'photonic nanoparticles' can be used to help treat cancer. These particles have special properties that allow them to be used with special light to treat cancer. However, the size of the particles is really important, so scientists are trying to find ways to make sure they are the right size. There are also some challenges with using these particles in people, like making sure they don't harm the body and that they go to the right place. Scientists are working on ways to improve the safety of these particles and make sure they go where they need to.


Metal Nanoparticles , Nanoparticles , Neoplasms , Humans , Precision Medicine , Optics and Photonics , Theranostic Nanomedicine , Neoplasms/diagnosis , Neoplasms/drug therapy
9.
Article En | MEDLINE | ID: mdl-37186179

Since the solar irradiation is accessible in many parts of our planet, it is a viable replacement for fossil fuels, so commissioning photovoltaic (PV) power plants are increased, rapidly. One of the main problems that this technology faces is the increase in the temperature of solar cells. In this paper, streaming water layer over the upper side of PV modules is considered as a cooling method. This technique not only lowers the surface temperature, but also keeps the surface clean. Four different water flow rates of 0.5, 1, 2, and 4 lit/min were used so that two different flow patterns, water streaks and water film, were formed. In addition, the negative effect of the residual water layer over the surface of the PV panel on the absorbed radiation was evaluated experimentally. As results, temperature drops of 20.6 °C and 29.7 °C were measured for flow rates of 0.5 and 2 lit/min, respectively. Also, for the case of 4 lit/min, the efficiency is increased by 6.7% compared to the conventional case. Moreover, it was observed that after the formation of a water layer, the water flow rate no longer has a significant effect on cooling. Finally, a comparison between the electrical efficiency enhancements of this study with those of similar researches was performed.

10.
Article En | MEDLINE | ID: mdl-36952170

Modification of photocatalysts to improve their adsorption and photocatalytic activity in the oxidative desulfurization of liquid fuels has been reported by many investigators. In this study, Pt-decorated carbon-doped TiO2 nanoparticles were synthesized by hydrothermal and photo-deposition techniques and were subsequently used in photocatalytic oxidative desulfurization of dibenzothiophene (DBT) in n-heptane as a simulated liquid fuel with methanol as the extracting solvent. Carbon-doped TiO2 was first synthesized by a simple self-doping method. Pt was then loaded by a photo-deposition technique. The synthesized photocatalysts (labeled as YPt-CT where Y is percent Pt loading) were characterized by of X-ray diffraction (XRD), photoluminescence (PL), field emission scanning electron microscopy (FESEM), N2-physisorption, UV-Vis diffusive reflectance spectra (UV-Vis DRS), transmission electron microscopy (TEM), Fourier transform infrared spectra (FTIR), and nitrogen sorption measurements. The removal efficiency of DBT was 98% in the presence of 2 g/l of 0.5Pt-CT catalyst under visible-light irradiation (λ > 400 nm), ambient pressure, and reaction temperature of 40°C.

11.
Gene ; 865: 147292, 2023 May 20.
Article En | MEDLINE | ID: mdl-36854347

Uterine leiomyomas (ULs) are benign solid tumors arising from the uterine myometrium. They are the most common pelvic tumors among females of reproductive age. Despite the universal prevalence of ULs and its huge impact on women's lives, the exact etiology and pathophysiologic mechanisms have not been fully understood. Numerous studies indicate that genetic factors play a crucial role in ULs development. This study aims to identify the probable genetic causes of ULs in a consanguineous Iranian family. Whole-exome sequencing (WES) on five family members with ULs revealed a likely pathogenic missense variant encoding for Y88C in the transactivation (TA) domain of DLX3 gene (c.263A > G; p.Y88C). Sanger sequencing of a total of 9 affected and non-affected family members indicated a segregation with disease with autosomal dominant inheritance. Moreover, targeted Sanger sequencing on 32 additional non-related patients with ULs showed none was heterozygous for this variant. MutPred2 predicted the pathogenicity of candidate variant by both phosphorylation and sulfation loss as actionable hypotheses. Project HOPE revealed that the identified variant residue is smaller and more hydrophobic comparing to the wild-type residue. I-TASSER and UCSF Chimera were also used for modeling and visualizing the predicted variant, respectively. This WES analysis is the first to report a variant in DLX3 variation associated with ULs pathogenicity in Iranian population highlighting the effectiveness of WES as a strong diagnostic method. However, further functional studies on this variant are needed to confirm the potential pathogenicity of this mutation.


Abortion, Spontaneous , Leiomyoma , Female , Humans , Pregnancy , Consanguinity , Iran , Leiomyoma/genetics , Mutation , Mutation, Missense , Pedigree
12.
CNS Neurol Disord Drug Targets ; 22(1): 51-65, 2023.
Article En | MEDLINE | ID: mdl-35249508

Neuropsychiatric disorders that affect the central nervous system cause considerable pressures on the health care system and have a substantial economic burden on modern societies. The present treatments based on available drugs are mostly ineffective and often costly. The molecular process of neuropsychiatric disorders is closely connected to modifying the genetic structures inherited or caused by damage, toxic chemicals, and some current diseases. Gene therapy is presently an experimental concept for neurological disorders. Clinical applications endeavor to alleviate the symptoms, reduce disease progression, and repair defective genes. Implementing gene therapy in inherited and acquired neurological illnesses entails the integration of several scientific disciplines, including virology, neurology, neurosurgery, molecular genetics, and immunology. Genetic manipulation has the power to minimize or cure illness by inducing genetic alterations at endogenous loci. Gene therapy that involves treating the disease by deleting, silencing, or editing defective genes and delivering genetic material to produce therapeutic molecules has excellent potential as a novel approach for treating neuropsychiatric disorders. With the recent advances in gene selection and vector design quality in targeted treatments, gene therapy could be an effective approach. This review article will investigate and report the newest and the most critical molecules and factors in neuropsychiatric disorder gene therapy. Different genome editing techniques available will be evaluated, and the review will highlight preclinical research of genome editing for neuropsychiatric disorders while also evaluating current limitations and potential strategies to overcome genome editing advancements.


Genetic Therapy , Mental Disorders , Humans , Mental Disorders/genetics , Mental Disorders/therapy
13.
Cell Tissue Bank ; 24(2): 307-315, 2023 Jun.
Article En | MEDLINE | ID: mdl-36074213

PURPOSE: Platelet-rich plasma (PRP) is a remarkable substance, which involves the growth and proliferation of all cell types. As a source of growth factors, we evaluated whether sperm cryopreservation supplemented with PRP improves the rates of sperm motility, viability, and DNA integrity after vitrification compared with conventional cryo-medium. MATERIALS AND METHODS: 20 normal semen specimens were collected from healthy men. After swim-up preparation, each sample was divided into four aliquots. One, as control, received no treatment, and the other three experimental samples were treated with three different concentrations of PRP as cryoprotectant. Sperm parameters were examined before and after freezing procedure. RESULTS: PRP had no significant effect on sperm count. Meanwhile, the percentage of sperm progressive motility and viability in the PRP treated samples with 1×105 /µL concentration was significantly higher than control group. Besides, the rate of immotile sperms in these samples was significantly lower than the control. Sperm viability was significantly higher in the PRP samples at 1×105/µL concentration. In the case of DNA integrity, CMA3 staining showed that the lower PRP concentration was correlated with the higher rate of abnormal spermatozoa. SCD showed that the rate of abnormal sperms in the PRP samples with 1×105 /µL concentration was significantly lower than control group. CONCLUSIONS: This study showed a protective effect of PRP on human sperm quality at an optimized concentration after vitrification. Besides, the effects of PRP supplementation of sperms on successful fertility following sperm preservation will be of interest.


Platelet-Rich Plasma , Semen , Humans , Male , Sperm Motility , Spermatozoa , Cryoprotective Agents/pharmacology , Dietary Supplements
14.
Med Oncol ; 39(5): 91, 2022 May 15.
Article En | MEDLINE | ID: mdl-35568790

Glioblastoma multiforme (GBM) grade IV glioma is the most frequent and deadly intracranial cancer. This tumor is determined by unrestrained progression, uncontroled angiogenesis, high infiltration and weak response to treatment, which is chiefly because of abnormal signaling pathways in the tumor. A member related to the Cap 'n' collar family of keypart-leucine zipper transcription agents-the transcription factor NF-E2-related factor 2 (Nrf2)-regulates adaptive protection answers by organized upregulation of many genes that produce the cytoprotective factors. In reply to cellular pressures types such as stresses, Nrf2 escapes Kelch-like ECH-related protein 1 (Keap1)-facilitated suppression, moves from the cytoplasm towards the nucleus and performs upregulation of gene expression of antioxidant responsive element (ARE). Nrf2 function is related tocontrolling many types of diseases in the human specially GBM tumor.Thus, we will review the epigeneticalregulatory actions on the Nrf2/Keap1 signaling pathway and potential therapeutic options in GBM by aiming the stimulation of Nrf2.


Glioblastoma , NF-E2-Related Factor 2 , Antioxidants/pharmacology , Glioblastoma/drug therapy , Glioblastoma/genetics , Humans , Kelch-Like ECH-Associated Protein 1/genetics , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Signal Transduction
15.
Cell Tissue Bank ; 23(4): 923-936, 2022 Dec.
Article En | MEDLINE | ID: mdl-35590084

The aim of this research is to compare the capabilities of Adipose tissue mesenchymal stem cells (AT-MSCs) and bone marrow mesenchymal stem cells (BM-MSCs) in the treatment of diabetic male mice with CLI model. Supernatants were collected from C57BL/6 mice isolated AT-MSCs and BM-MSCs, afterward their effects on human umbilical vein endothelial (HUVEC) migration potential were evaluated. Diabetes mellitus type 1 was induced by streptozotocin injection. Diabetic mice with CLI model were divided into three groups and injected with AT-MSCs, BM-MSCs, or PBS then the efficacy of them was assessed. Survival of MSCs was analysed by SRY-specific gene. The conditioned medium of AT-MSCs and BM-MSCs stimulated HUVECs migration and the donor cells were detected till 21 day in two groups. BM-MSCs and AT-MSCs improved significantly functional recovery and ischemia damage. Neovascularization in ischemic muscle was significantly higher in mice treated with AT-MSCs and BM-MSCs and they improved muscle regeneration. In vivo and in vitro findings show that AT-MSCs and BM-MSCs transplantation could be proposed as a promising therapy to promote angiogenesis and muscle regeneration through secretion of proangiogenic factors, cytokines and growth factors in diabetic mice with CLI model wherein blood supply is insufficient and disrupted.


Diabetes Mellitus, Experimental , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Humans , Mice , Male , Animals , Neovascularization, Physiologic , Diabetes Mellitus, Experimental/therapy , Diabetes Mellitus, Experimental/metabolism , Chronic Limb-Threatening Ischemia , Mice, Inbred C57BL , Mesenchymal Stem Cells/metabolism , Ischemia/therapy , Ischemia/metabolism , Adipose Tissue
16.
J Wound Care ; 30(Sup9a): XIIIi-XIIIx, 2021 Sep 02.
Article En | MEDLINE | ID: mdl-34597172

OBJECTIVE: Providing a suitable environment to improve the healing process is the main target of wound dressing that also protects the wound from additional harms. In the present study, fabrication and characterisation of a new kind of electrospun wound dressing composed of polyvinyl alcohol (PVA) and quince seed mucilage (QSM) is reported. METHOD: QSM was extracted from quince seeds, purified, freeze-dried and used to produce aqueous solutions containing different amounts of PVA and QSM. The wound dressings were fabricated via the electrospinning method and their characteristics were investigated with scanning electron microscope (SEM) images, Fourier transform infrared (FTIR) spectra, tensile and swelling test, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cytotoxicity assay against fibroblast cells. RESULTS: SEM images confirmed that proper, uniform, non-oriented nanofibres with an average diameter in the range of 60-240nm, depending on the QSM content had been fabricated. The tensile test showed that with increasing QSM content, the tensile strength of fibre increased while elongation at break was decreased, which was consistent with SEM images where the diameter of samples decreased by increasing QSM content. MTT assay showed significant biocompatibility against fibroblast cells; however, it was increased by increased QSM proportion. In addition, SEM images supported the proper adhesion of fibroblast cells on the sample one day after culturing. CONCLUSION: Overall, the findings of the current study support the potential of PVA/QSM nanofibres as a proper candidate for biomedical applications, especially as a wound dressing.


Polyvinyl Alcohol , Rosaceae , Bandages , Seeds , Wound Healing
17.
Future Oncol ; 17(29): 3873-3880, 2021 Oct.
Article En | MEDLINE | ID: mdl-34263659

The mortality and morbidity rates for prostate cancer have recently increased to alarming levels, rising higher than lung cancer. Due to a lack of drug targets and molecular probes, existing theranostic techniques are limited. Human LIN28A and its paralog LIN28B overexpression are associated with a number of tumors resulting in a remarkable increase in cancer aggression and poor prognoses. The current review aims to highlight recent work identifying the key roles of LIN28A and LIN28B in prostate cancer, and to instigate further preclinical and clinical research in this important area.


Molecular Targeted Therapy , Precision Medicine , Prostatic Neoplasms/therapy , RNA-Binding Proteins/metabolism , Humans , Male , Prostatic Neoplasms/pathology
18.
Life Sci ; 278: 119632, 2021 Aug 01.
Article En | MEDLINE | ID: mdl-34019900

Diabetes epidemiological quantities are demonstrating one of the most important communities' health worries. The essential diabetic difficulties are including cardiomyopathy, nephropathy, inflammation, and retinopathy. Despite developments in glucose decreasing treatments and drugs, these diabetic complications are still ineffectively reversed or prohibited. Several signaling and molecular pathways are vital targets in the new therapies of diabetes. This review assesses the newest researches about the key molecules and signaling pathways as targets of molecular pharmacology in diabetes and diseases related to it for better treatment based on molecular sciences. The disease is not cured by current pharmacological strategies for type 2 diabetes. While several drug combinations are accessible that can efficiently modulate glycemia and mitigate long-term complications, these agents do not reverse pathogenesis, and in practice, they are not established to modify the patient's specific molecular profiling. Therapeutic companies have benefited from human genetics. Genome exploration, which is agnostic to the information that exists, has revealed tens of loci that impact glycemic modulation. The physiological report has begun to examine subtypes of diseases, illustrate heterogeneity and propose biochemical therapeutic pathways.


Diabetes Complications/drug therapy , Diabetes Mellitus/drug therapy , Drug Discovery , Molecular Targeted Therapy , Signal Transduction/drug effects , Animals , Diabetes Complications/genetics , Diabetes Complications/metabolism , Diabetes Complications/pathology , Diabetes Mellitus/genetics , Diabetes Mellitus/metabolism , Diabetes Mellitus/pathology , Humans , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use
19.
Reprod Sci ; 28(7): 2050-2059, 2021 07.
Article En | MEDLINE | ID: mdl-33683669

Injection of intraovarian platelet-rich plasma (PRP) was recently presented in terms of improvement ovarian function in women with a poor ovarian response (POR) or primary ovarian insufficiency (POI). In a before and after study, 17 poor responder women and 9 women with the diagnosis of POI were recruited. The multifocal intramedullary infusion of 1.5 ml activated PRP was performed into each ovary. The majority of women in both groups received the second PRP injection with the twofold increase in the dosage to 3ml, 3 months after the first injection. Evaluation of serum anti-mullerian hormone ( AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) was performed. In addition, all women were followed with regard to pregnancy outcome up to delivery. In the POI group, menstrual restoration was monitored. The significant difference was not detected regarding the hormonal profile between the three time points in both groups. With regard to pregnancy outcome, 8/17 (47%) of PORs had spontaneous pregnancy in response to PRP injection. Of those, three women (37.55%) had abortions, whereas 4 pregnancies (50%) led to healthy live births, and one woman (12.5%) was in the 24th week of her pregnancy. Menstruation recovery occurred among 22.2% of women with POI after the second PRP injection, but no one became pregnant. Intraovarian injection of autologous PRP might be considered an alternative treatment in poor responders. As for women with POI, it is questionable whether PRP could induce menstrual recovery.


Ovarian Reserve/physiology , Ovary/drug effects , Platelet-Rich Plasma , Primary Ovarian Insufficiency/physiopathology , Adult , Anti-Mullerian Hormone/blood , Estradiol/blood , Female , Fertilization in Vitro , Follicle Stimulating Hormone/blood , Humans , Luteinizing Hormone/blood , Ovary/physiopathology , Pregnancy , Pregnancy Outcome , Primary Ovarian Insufficiency/blood , Rejuvenation
20.
Ther Deliv ; 12(3): 235-244, 2021 03.
Article En | MEDLINE | ID: mdl-33624533

The COVID-19 pandemic continues to endanger world health and the economy. The causative SARS-CoV-2 coronavirus has a unique replication system. The end point of the COVID-19 pandemic is either herd immunity or widespread availability of an effective vaccine. Multiple candidate vaccines - peptide, virus-like particle, viral vectors (replicating and nonreplicating), nucleic acids (DNA or RNA), live attenuated virus, recombinant designed proteins and inactivated virus - are presently under various stages of expansion, and a small number of vaccine candidates have progressed into clinical phases. At the time of writing, three major pharmaceutical companies, namely Pfizer and Moderna, have their vaccines under mass production and administered to the public. This review aims to investigate the most critical vaccines developed for COVID-19 to date.


COVID-19 Vaccines , COVID-19/prevention & control , Humans , Pandemics
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