Muhammad Zahoor

Mastitis is a common inflammation of mammary glands that has a significantly impact on dairy production and animal health, causing considerable economic burdens worldwide. Elevated reactive oxygen species (ROS) followed by oxidative stress, apoptosis, inflammatory changes and suppressed immunity are considered the key biomarkers observed during mastitis. The Nrf2/KEAP1 signaling pathway plays a critical role in regulating antioxidant responses and cellular defense mechanisms. When activated by bioactive compound treatment, Nrf2 translocates to the nucleus and induces the expression of its target genes to exert antioxidant responses. This reduces pathogen-induced oxidative stress and inflammation by inhibiting NF-kB signaling in the mammary glands, one of the prominent pro-inflammatory signaling pathway. Here, we summarize recent studies to highlight the therapeutic potential of Nrf2/KEAP1 pathway in the prevention and treatment of mastitis. Collectively this review article aims to explore the potential of bioactive compounds in mitigating mastitis by targeting the Nrf2/KEAP1 signaling pathway.

The reproductive efficiency of livestock is crucial for agricultural productivity and economic sustainability. One critical factor in successful fertilization and the viability of offspring is the quality of semen. Poor semen quality, especially in frozen-thawed semen used in artificial insemination (AI) have been shown to influence conception outcomes, resulting a negative impact on livestock production. Recent advancements in genetic research have identified specific markers linked to semen quality traits in various livestock species, such as cattle, sheep, goats, pigs, buffalo, and equines. These genetic markers are essential in screening males for breeding suitability, which in turn enhances selective breeding programs. Understanding these markers is crucial for improving reproductive performance and increasing productivity in livestock populations. This review offers a comprehensive overview of the genetic markers associated with semen quality in key livestock. It explores the underlying genetic mechanisms and their practical implications in animal breeding and management. The review underscores the importance of integrating genetic insights into breeding strategies to optimize reproductive efficiency and ensure the sustainable development of livestock industries.

Extracellular vesicles (EVs) have emerged as key intercellular communication and pathogenesis mediators. Parasitic organisms’ helminths, cause widespread infections with significant health impacts worldwide. Recent research has shed light on the role of EVs in the lifecycle, immune evasion, and disease progression of these parasitic organisms. These tiny membrane-bound organelles including microvesicles and exosomes, facilitate the transfer of proteins, lipids, mRNAs, and microRNAs between cells. EVs have been isolated from various bodily fluids, offering a potential diagnostic and therapeutic avenue for combating infectious agents. According to recent research, EVs from helminths hold great promise in the diagnosis of parasitic infections due to their specificity, early detection capabilities, accessibility, and the potential for staging and monitoring infections, promote intercellular communication, and are a viable therapeutic tool for the treatment of infectious agents. Exploring host-parasite interactions has identified promising new targets for diagnostic, therapy, and vaccine development against helminths. This literature review delves into EVS’s origin, nature, biogenesis, and composition in these parasitic organisms. It also highlights the proteins and miRNAs involved in EV release, providing a comprehensive summary of the latest findings on the significance of EVs in the biology of helminths, promising targets for therapeutic and diagnostic biomarkers.

Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body’s antioxidant defenses. It poses a significant threat to the physiological function of reproductive cells. Factors such as xenobiotics and heat can worsen this stress, leading to cellular damage and apoptosis, ultimately decreasing reproductive efficiency. The nuclear factor erythroid 2–related factor 2 (Nrf2) signaling pathway plays a crucial role in defending against oxidative stress and protecting reproductive cells via enhancing antioxidant responses. Dysregulation of Nrf2 signaling has been associated with infertility and suboptimal reproductive performance in mammals. Recent advancements in therapeutic interventions have underscored the critical role of Nrf2 in mitigating oxidative damage and restoring the functional integrity of reproductive cells. In this narrative review, we delineate the harmful effects of heat and xenobiotic-induced oxidative stress on reproductive cells and explain how Nrf2 signaling provides protection against these challenges. Recent studies have shown that activating the Nrf2 signaling pathway using various bioactive compounds can ameliorate heat stress and xenobiotic-induced oxidative distress and apoptosis in mammalian reproductive cells. By comprehensively analyzing the existing literature, we propose Nrf2 as a key therapeutic target for mitigating oxidative damage and apoptosis in reproductive cells caused by exposure to xenobiotic exposure and heat stress. Additionally, based on the synthesis of these findings, we discuss the potential of therapies focused on the Nrf2 signaling pathway to improve mammalian reproductive efficiency.

Backgrounds: Multiple myeloma (MM), one of the most prevalent hematological malignancies, is characterized by the proliferation of plasma cells within bone marrow and concurrent development of osteolytic lesions. The persistence of myeloma cells in the hypoxic bone marrow environment, coupled with their resistance to current therapeutic approaches, often results in relapse. Hence, there is an immediate imperative to decipher the molecular mechanisms underpinning myelomagenesis to pave the way for more efficacious treatment modalities. While prior investigations have predominantly focused on delineating the roles of individual genes in myelomagenesis, this article offers a comprehensive analysis of the current research landscape encompassing four distinct oncogenic gene signatures and their impact on patients' survival outcomes. Methods: We utilized the most robust RNAseq datasets, GSE13591 and Compass AI8 to evaluate hypoxia, MM bone disease (MBD), dormancy and para-inflammation genes signatures. Fisher's least significant difference post hoc tests were used to determine significance between MM groups while Spearman R-value was calculated to assess regression and correlation among each gene signature. Each signature was grouped as Low and high expression based on median and survival outcomes was plotted using the Kaplan Meier. Results: Through the collective analysis of these gene signatures, we gain invaluable insights into the intricate molecular cues that initiate and propel MM progression. Furthermore, this article sheds light on the intricate interplay among these oncogenic gene signatures, illustrating how they intersect and synergistically influence MM's pathogenesis. Conclusion: In conclusion, this article underscores the paramount importance of a comprehensive examination of the four oncogenic gene signatures associated with myelomagenesis. By considering their collective impact on patient survival and elucidating their intricate interrelationships, we significantly augment our understanding of the complex molecular landscape governing MM.

Introduction: Polycystic Ovarian Syndrome (PCOS) is a globally prevalent condition that leads to infertility in women. While environmental factors contribute to PCOS, maternal genetics also play a significant role. Currently, there is no definitive test for identifying predisposition to PCOS. Hence, our objective is to discover novel maternal genetic risk factors for PCOS by investigating the genomes of patients from Pakistan.Methods: We utilized Next-Generation Sequencing (NGS) to sequence the complete mitochondrial DNA of three PCOS patients. Subsequently, we employed MitoTIP (Mitochondrial tRNA Informatics Predictor) and PON-mt-tRNA tools to identify variations in the mitochondrial DNA. Our analysis focused on the genes MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB, which displayed common variations in all three genomes. Additionally, we observed individual variations. The D-loop region exhibited the highest frequency of mutations, followed by the non-coding regions of RNR1 and RNR2 genes. Moreover, we detected frameshift mutations in the mitochondrially encoded NADH Dehydrogenase 2 (MT-ND2) and mitochondrially encoded NADH Dehydrogenase 5 (ND5) genes within individual genomes.Results: Our analysis unveiled six regions with common variations in the mitochondrial DNA of all three PCOS patients. Notably, the MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB genes exhibited these variations. Additionally, we identified individual variations in the mitochondrial DNA. The D-loop region displayed the highest mutation frequency, followed by the non-coding regions of RNR1 and RNR2 genes. Furthermore, frameshift mutations were detected in the MT-ND2 and ND5 genes within individual genomes.Conclusion: Through our study, we have identified variations in mitochondrial DNA that may be associated with the development of PCOS and have the potential to serve as predisposition tests. Our findings highlight the presence of novel mutations in the MT-RNR1, MT-RNR2, MT-ATP6, MT-TL2, and MT-CYTB genes, as well as frameshift mutations in the MT-ND2 and ND5 genes. Pathogenicity analysis indicated that most variants were likely to result in benign cysts. However, the frameshift mutations in the ND2 gene were associated with a high risk of complications and pathogenicity in PCOS. This is the first report identifying these mutations and their association with PCOS, contributing to our understanding of the genetic factors underlying the condition.

Mammary glands are known for their ability to convert nutrients present in the blood into milk contents. In cows, milk synthesis and the proliferation of cow mammary epithelial cells (CMECs) are regulated by various factors, including nutrients such as amino acids and glucose, hormones, and environmental stress. Amino acids, in particular, play a crucial role in regulating cell proliferation and casein synthesis in mammalian epithelial cells, apart from being building blocks for protein synthesis. Studies have shown that environmental factors, particularly heat stress, can negatively impact milk production performance in dairy cattle. The mammalian target of rapamycin complex 1 (mTORC1) pathway is considered the primary signaling pathway involved in regulating cell proliferation and milk protein and fat synthesis in cow mammary epithelial cells in response to amino acids and heat stress. Given the significant role played by the mTORC signaling pathway in milk synthesis and cell proliferation, this article briefly discusses the main regulatory genes, the impact of amino acids and heat stress on milk production performance, and the regulation of mTORC signaling pathway in cow mammary epithelial cells.

Biomaterials are in use for the replacement and reconstruction of several tissues and organs as treatment and enhancement. Metallic, organic, and composites are some of the common materials currently in practice. Metallic materials contribute a big share of their mechanical strength and resistance to corrosion properties, while organic polymeric materials stand high due to their biocompatibility, biodegradability, and natural availability. To enhance the biocompatibility of these metals and alloys, coatings are frequently applied. Organic polymeric materials and ceramics are extensively utilized for this purpose due to their outstanding characteristics of biocompatibility and biodegradability. Hydroxyapatite (HAp) is the material from the ceramic class which is an ultimate candidate for coating on these metals for biomedical applications. HAp possesses similar chemical and structural characteristics to normal human bone. Due to the bioactivity and biocompatibility of HAp, it is used for bone implants for regenerating bone tissues. This review covers an extensive study of the development of HAp coatings specifically for the orthopaedic applications that include different coating techniques and the process parameters of these coating techniques. Additionally, the future direction and challenges have been also discussed briefly in this review, including the coating of HAp in combination with other calcium magnesium phosphates that occur naturally in human bone.