Pharmaceutical Sciences
Volume:29 Issue: 4, Oct 2023

An immune system response known as inflammation can be carried on by a variety of things, such as infections, damaged cells, and noxious substances. These factors may cause acute or chronic inflammatory responses in the heart, pancreas, liver, kidney, lungs, brain, colon, and reproductive system, which may cause disease or tissue damage. Inflammatory cells and signaling pathways are activated by both pathogenic and non-pathogenic agents, cell injury, and infectious agents. The most ubiquitous types of these include tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), High mobility group box 1 protein (HMGB1), mitogen-activated protein kinase (MAPK), monocyte chemoattractant protein (MCP1), interleukin 1 beta (IL1β), and Janus kinase-signal transducer and activator of transcription (JAK-STAT). Severe inflammation has the potential to cause systemic inflammatory response syndrome. The most severe forms of this condition are characterized by hyperinflammation and can cause organ damage, shock, and even death. We concentrate on the origin of inflammation, all conceivable inflammatory mechanisms, and organ-specific inflammatory responses in this study on inflammatory reactions inside organs.

 Clinical studies, investigating the effect of β-Alanine (BA) supplementation on recovery biomarkers in physically active individuals, have generated inconsistent results. This systematic review and meta-analysis study aimed to clarify the clinically relevant dietary effects of BA supplementation.

 A comprehensive search was done in the electronic databases of Scopus, PubMed, ISI Web of Science and Embase from inception to 2022. Meta-analysis was done using the random-effects model. Pooled effect size was evaluated using standard mean difference (SMD) and 95% confidence intervals (CI). Heterogeneity of between-study was evaluated according to Cochran’s Q test and I2 . Subgroup analysis was conducted to identify the potential sources of heterogeneity.

 Overall, 32 studies were included in the current study. The results suggested that BA supplementation increases carnosine level significantly (SMD: 0.22mmol/L, 95%CI: -0.17, 0.61, P=0.27) but no effect was shown about lactate, fatigue, VO2 , pH and bicarbonate (HCO3 - ) (P>0.05). Subgroup analysis revealed a significant association of VO2, carnosine and fatigue with supplementation dosage, gender and duration of administration respectively.

 BA supplementation emerged its beneficial effects on enhancing carnosine level which highlights its ergogenic effects. In contrast, no significant effects had been shown in term of fatigue delay and blood levels of lactate, HCO3 - , pH, and VO2 value. These results warrant more investigation in a prospective design to clarify the exact mechanism in this way.

There has been increasing interest in studying the effects of dietary factors on telomere length. The telomere is a noncoding DNA sequence including “TTAGGG” at the ends of chromosomes of vertebrates. The stability of telomere length is an important factor as a survival signal for cells and cancer prevention. Telomerase is a multi-subunit DNA polymerase that plays a crucial role in maintaining the telomere length, which is critical for the age-related pathogenesis of breast neoplasm. Some regulatory factors interfere with telomerase activity and therefore promote breast tumorigenesis. High telomerase activity and restoring telomere lengths are determined as key factors in progressing tumors to advanced stages of malignancies, which are highly estrogen-dependent in breast carcinogenesis. Melatonin is a hormone-like substance secreted by the pineal gland and has been reported to downregulate telomerase. It may therefore control telomere length in cancer cells. Certain malignancy-related biological pathways have recently been linked to telomere length, and this review provides new insights regarding the effects of melatonin on telomere length by reviewing the anticarcinogenic mechanisms underlying melatonin in relation to telomerase activity in breast carcinogenesis. Experimental insights presenting the effects of melatonin alone or in combination with drugs on enhancing therapeutic protocols were also reviewed, which could assist our understanding of this hormone-like substance and telomeres as prognostic and therapeutic biomarkers in breast cancer.

 The exploration of bryophytes biodiversity in Indonesia due to its abundance and the bioactivity of its phytochemical content, such as alkaloids and polyphenols, has received increased interest. Despite some species proven to possess pharmacological properties, the antiproliferative study of Indonesian native moss, such as the Pogonatum genus, is limited. Hence, this study aims to evaluate the anticancer effects of Pogonatum neesii Dozy antiproliferative activity on colon and cervical cancer through in silico and in vitro methods.

 Molecular docking analysis using Autodock VINA in PyRx softwre was conducted between natural compounds found on P. neesii and several target proteins, DNA (cytosine-5)- methyltransferase 1 (DMT-1) (Protein Data Bank (PDB) id: 4WXX) in colon cancer and B-cell lymphoma 2 (Bcl-2) (PDB id: 4LXD) in cervical cancer. Afterwards, total phenolic and alkaloid contents were measured. Subsequently, P. neesii was tested on HaCaT (keratinocytes), HEK293 (human embryonic kidney), HT-29 (colorectal cancer models) and HeLa (cervical cancer model) to observe its cytotoxicity.

 Out of eight compounds, chlorogenate was found to exert the best binding energy with target proteins, although it had lower binding affinity than the protein’s natural ligand. However, the biological, drug-likeness, and toxicity analysis suggested the drug potency of the compound, thus we did the in vitro analysis. P. neesii showed significant cytotoxic effects on HT-29 and HeLa cells, while it did not exert any cytotoxic effects on HaCaT and HEK-293 cells, at the same concentrations.

 P. neesii has been shown to have the potential as an anticancer agent through in silico and in vitro analysis, where the extract showed selective cytotoxicity towards cancer cell lines and cytocompatibility towards normal cell lines. Chlorogenate was pinpointed as the compound with the most activity and interaction with the target proteins in both cancers.

 Clozapine (CLZ) and risperidone (RIS) are drugs that have the ability to disrupt mitochondrial function. Also, these drugs increase the level of free radicals. Mitochondrial dysfunction plays a role in the etiology of various diseases. Replacement and treatment of defective mitochondria with healthy mitochondria have been considered. Mitochondrial therapy (mitotherapy) or exogenous mitochondria transplantation is a method that can be used to replace dysfunctional mitochondria with healthy mitochondria. This method can help in the treatment of diseases related to mitochondria.

 In this study, we investigated the transplantation effect of isolated lymphocyte mitochondria on the toxicity induced by CLZ and RIS on human blood lymphocytes. Lymphocytes were isolated using the Ficoll standard method. Mitochondria of human lymphocytes were used for mitotherapy. This study was conducted in 6 groups. After treatment, the level of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), reduced glutathione (GSH) content, oxidized glutathione (GSSG) content, and adenosine triphosphate (ATP) content were evaluated.

 Our data showed that CLZ (70 µm) and RIS (24 nM) caused cytotoxicity on human blood lymphocytes which are associated with ROS generation, collapse in MMP, decrease in GSH content, increase in GSSG content and change in ATP content. Mitochondria transplantation results showed that adding mitochondria of lymphocytes could protect the lymphocytes against the toxicity effects caused by CLZ and RIS. Furthermore, the results showed that pre-incubation with cytochalasin D considerably reserved the protective effects of mitotherapy in the human lymphocytes.

 We proposed that mitochondria transplantation or mitotherapy-affected blood lymphocytes with exogenous mitochondria could be used to treat CLZ and RIS-induced toxicity.

 Group B Streptococcus (GBS) is a bacterium commonly isolated from the vagina. Silver nanoparticles (SNPs) are potential antibacterial agents, and studies have shown their toxic effects. Vitamin C (VC) is an essential vitamin with a protective role against toxicological conditions. We aimed to the evaluation therapeutic effects of the co-administration of SNPs and VC on vaginal infection caused by GBS in mice models.

 Vaginitis model was established by intravaginal inoculation of GBS. The Co-administration of SNPs and VC was used to treat the infections. The antibacterial activity of SNPs was determined by the minimum inhibitory concentration. The toxicity of nanoparticles was measured by MTT assay. The microbial load and estrous cycle of mice during treatment were evaluated. Finally, blood samples and vaginal tissue sections were isolated and analyzed.

 The results showed that SNPs have excellent effects on GBS, and the MIC was 512 ppm. Cell viability after exposure at 512 ppm of SNPs was 32.11% but after treatment with VC increased viability at 512 ppm of nanoparticles to 65.32%. In mice that received SNPs and VC at the same time, the bacteria were completely removed from the vagina, and estrus cycle returned to normal cycle. Analysis of the prepared blood samples and microscopic examination of the vaginal sections confirmed the results.

 SNPs have a potential antibacterial effect on GBS. But nanoparticles have toxic effects on mammalian cells. The simultaneous use of VC, as a powerful antioxidant, can completely eliminate this toxic effect of nanoparticles.

 Mesenchymal stem cells (MSCs) are undifferentiated cells with the ability of multi-potency, pluripotency, and self-renewal. MSCs show great promise in cancer therapy due to their unique features. MSC secrete various cytokines with multifunctional properties, although their roles are unclear.

 We have investigated the influence of secreted cytokines from MSCs on KG-1 cells as a cell model of acute myeloid leukemia (AML). For this purpose, following the culture and characterization of MSCs, a trans-well system was used for co-culturing MSCs and KG-1. To determine apoptosis induction Ki/Caspase-3 assay was conducted for cultured KG-1 alone and in co-culture with MSCs (10:1) on day 7. In the following step, the protein was isolated from both groups (control and experimental) and western blotting was done for investigating the BAX and BCL-2 proteins expression.

 It was found that MSCs significantly enhanced caspase-3 activity in KG-1 cells (P<0.05). Besides, A significant increase in protein expression of BAX was detected, while BCL-2 displayed a dramatic reduction (P<0.01).

 As a concluding remark, MSCs have a contributory role in the apoptosis of KG-1 cells that is mediated by Caspase-3, BAX, and BCL2 expression.

 This research intended to discover the significance of miR-138 (microRNA 138) on the expression profile, proliferation, and the associated regulatory mechanisms in prostate cancer (PCa).

 Thirty-five specimens of prostate were studied to evaluate the expression level of miR138 by RT-qPCR (Quantitative reverse transcription polymerase chain reaction). Bioinformatics analysis was performed to search for the target genes of miR-138; and ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase), CCND1 (cyclin D1), CCND3 (cyclin D3), VIM (vimentin), TWIST1 (twist family bHLH transcription factor 1), HIF1A (hypoxia-inducible factor 1 subunit alpha), and TERT (telomerase reverse transcriptase) genes were selected. Then, the biological role of miR-138 and CCND1 in the progression of PCa was investigated using RT-qPCR and luciferase reporter gene assay. Finally, overexpression of miR-138 on the proliferation in PCa cell lines was analyzed using the MTT (3-(4, 5-dimethylthiazol-2-Yl)-2, 5-diphenyltetrazolium bromide, Sigma, Germany) assay.

 RT-qPCR showed that the expression of miR-138 downregulated in PCa tissues and cell lines. Bioinformatics analysis and RT-qPCR assay demonstrated that CCND1 expression level was negatively correlated with miR-138 in PCa tissues and the PC3 cell line. Moreover, CCND1 was predicted to be the target gene of miR138 in the PC3 cell line based on the results of luciferase reporter gene assay. Substantially, over-expression of miR138-5p mimic could inhibit the expression level of CCND1 gene in PC3 cell lines. Lastly, over-expression of miR-138 inhibited the proliferative capacities in PC3 and DU-145 cells.

 Our research introduces miR-138 as a negative regulator of CCND1 in the progression of PCa with an inhibitory impact on the proliferation rate of PCa cell lines. This regulatory mechanism could be utilized for the design and target selection of remedial miRNA-based approaches.

 Complex interplays happen in absorption and function of iron, zinc and copper. Both zinc deficiency and excess may lead to anemia. In Iran, commonly available supplements for chronic kidney disease (CKD) patients contain 25 mg-zinc (Zn). This study compared 25 mg versus 7.5 mg dose of zinc in anemia of CKD patients, the latter dose approximates to recommended dietary intake (RDI) of zinc.

 In this double-blinded clinical trial, 51 non-dialysis CKD patients were randomized to continue previous formulation (25 mg-Zn group) or change to a new preparation (7.5 mg-Zn group) for three months. Blood counts and serum iron, zinc and copper status were compared between and within the groups.

 At the end of the study, serum copper and ceruloplasmin concentrations were significantly higher in 7.5 mg-Zn group compared with those in 25 mg-Zn arm (115.04± 23.05 vs. 102.48±14.98 µg/dL; P= 0.02 and 29.97±7.94 vs. 25.42±4.23 mg/dL; P= 0.01, respectively). Serum zinc levels did not differ between two groups (76.73±15.35 vs. 77.68±18.07 µg/dL for 7.5 mg-Zn and 25 mg-Zn groups, respectively; P= 0.84). After three months, patients in 7.5 mg-Zn group experienced increase in their Hb (11.11±1.17 vs. 10.72±1.03 g/dL; P= 0.04), HCT (35.28± 4.01 vs. 33.96± 3.74%; P= 0.03), MCV (86.30 (81.40-90.82) vs. 86.00 (80.35-88.77) ¦L; P= 0.01) and ferritin (202.60 (79.29-298.97) vs. 129.07 (42.25-225.87) ng/mL; P<0.001) compared to their baseline values.

 Reducing zinc content to its RDI value in supplement for CKD patients led to increased serum copper and ceruloplasmin concentrations. Moreover, patients who switched to RDI zinc-containing formula experienced a significant rise in blood hemoglobin. hematocrit, mean corpuscular volume (MCV), and ferritin concentration.

 Pressure lesions are chronic wounds causing the development of infection and inflammation into deeper structures and finally necrosis. In Persian medicine, Alkanna orientalis (Boraginaceae) has been used for centuries as a naturally derived remedy for managing lesions. A cross-sectional pilot clinical trial was conducted to assess the wound healing effect of an ointment made of chloroform extract of roots of A. orientalis (CERAO).

 Sixty patients (36 men and 24 women) diagnosed with bedsore staging 1-2 entered the study for one year. They were divided into two groups of control and treatment with equal proportions. The control group received conventional treatment from the hospital, including irrigation serum, mupirocin, phenytoin ointments, and gauze dressing. After rinsing and cleansing with normal saline, in the intervention group, patients received a thin layer of CERAO once daily for four weeks. Clinical outcomes were measured at weeks 2 and 4.

 Recovery assessment was carried out by measuring wound area, days of epithelia formation, and complete wound closure. The difference between the two groups was statistically significant (P-value <0.05) in terms of the mentioned criteria. The recovery percentage was 26.7% and 60% for the control and treatment groups, respectively. In the control group, 16.7% of the study population experienced the development of wounds, while in the intervention group, wound progression was not observed.

 The results of this pilot study indicated that the clinical efficacy of CERAO could be promising and a replacement for conventional treatment of pressure ulcers.