Implications For Treatment Research Articles

Oronasal mucosal melanoma is defined by two transcriptional subtypes in humans and dogs with implications for diagnosis and therapy.

Mucosal melanoma is a rare melanoma subtype associated with a poor prognosis and limited existing therapeutic interventions, in part due to a lack of actionable targets and translational animal models for preclinical trials. Comprehensive data on this tumour type are scarce, and existing data often overlooks the importance of the anatomical site of origin. We evaluated human and canine oronasal mucosal melanoma (OMM) to determine whether the common canine disease could inform the rare human equivalent. Using a human and canine primary OMM cohort of treatment-naive archival tissue, alongside clinicopathological data, we obtained transcriptomic, immunohistochemical, and microbiome data from both species. We defined the transcriptomic landscape in both species and linked our findings to immunohistochemical, microbiome, and clinical data. Human and dog OMM stratified into two distinctive transcriptional groups, which we defined using a species-independent 41-gene signature. These two subgroups are termed CTLA4-high and MET-high and indicate actionable targets for OMM patients. To guide clinical decision-making, we developed immunohistochemical diagnostic tools that distinguish between transcriptomic subgroups. We found that OMM had conserved transcriptomic subtypes and biological similarity between human and canine OMM, with significant implications for patient classification, treatment, and clinical trial design. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Implications of a new clinical classification of acute myocardial infarction.

The diagnostic criteria for type 2 myocardial infarction identify a heterogenous group of patients with variable outcomes and no clear treatment implications. We aimed to determine the implications of a new clinical classification for myocardial infarction with more objective diagnostic criteria using cardiac imaging. In a prospective cohort study, patients with type 2 myocardial infarction underwent coronary angiography and cardiac magnetic resonance imaging or echocardiography. The new classification was applied to identify (a) spontaneous myocardial infarction due to acute coronary pathology, (b) secondary myocardial infarction precipitated by acute illness in the presence of obstructive coronary artery disease, a new regional wall motion abnormality or infarct pattern scarring, and (c) no myocardial infarction in the absence of obstructive disease or new myocardial abnormality. In 100 patients (65 years, 43% women) with type 2 myocardial infarction, the new classification identified 25 and 31 patients with spontaneous and secondary myocardial infarction, respectively, and 44 without myocardial infarction. Compared to patients without myocardial infarction, those with secondary myocardial infarction were older, had more risk factors, and higher troponin concentrations (P<0.05 for all). During a median follow up of 4.4 years, death, myocardial infarction or heart failure hospitalization was more common in secondary myocardial infarction compared to those without myocardial infarction (55% [17/31] versus 16% [7/44], P<0.001). A new clinical classification of myocardial infarction informed by cardiac imaging would reduce the diagnosis of myocardial infarction in acute illness and identify those patients at highest risk who are most likely to benefit from treatment. https://clinicaltrials.gov/ct2/show/NCT03338504.

A power dependence model of the impact of leader impostorism on supervisor support and undermining: The moderating role of power distance.

Leaders, often perceived as possessing exceptional confidence and competence, are not immune to feelings of self-doubt. Leader impostorism describes the experience that one's attributes, experiences, skills, and abilities fall short of the standards expected in the leadership role, resulting in a sense of deception in fulfilling leadership responsibilities. While existing research has examined the antecedents and individual outcomes of leader impostorism, its implications for leaders' treatment of subordinates remain largely unexplored. In this research, we investigate the downstream consequences of leader impostorism on behaviors directed toward subordinates. Integrating research on leader impostorism with power dependence theory, we propose that for leaders with a low power distance orientation, leader impostorism increases supervisor support through the mechanism of perceived power dependence on subordinates, whereas for leaders with a high power distance orientation, leader impostorism increases supervisor undermining through the mechanism of power threat. The findings from two field studies support our theoretical model. This research contributes to the literature by broadening the understanding of the impact of leader impostorism on subordinates, extending power dependence theory within leader-subordinate dynamics, and offering insights into the dual nature of impostorism and its contingent effects. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Synergistic and off-target effects of bacteriocins in a simplified human intestinal microbiome: implications for Clostridioides difficile infection control

ABSTRACT Clostridioides difficile is a major cause of nosocomial diarrhea. As current antibiotic treatment failures and recurrence of infections are highly frequent, alternative strategies are needed for the treatment of this disease. This study explores the use of bacteriocins, specifically lacticin 3147 and pediocin PA-1, which have reported inhibitory activity against C. difficile. We engineered Lactococcus lactis strains to produce these bacteriocins individually or in combination, aiming to enhance their activity against C. difficile. Our results show that lacticin 3147 and pediocin PA-1 display synergy, resulting in higher anti-C. difficile activity. We then evaluated the effects of these L. lactis strains in a Simplified Human Intestinal Microbiome (SIHUMI-C) model, a bacterial consortium of eight diverse human gut species that includes C. difficile. After introducing the bacteriocin-producing L. lactis strains into SIHUMI-C, samples were collected over 24 hours, and the genome copies of each species were assessed using qPCR. Contrary to expectations, the combined bacteriocins increased C. difficile levels in the consortium despite showing synergy against C. difficile in agar-based screening. This can be rationally explained by antagonistic inter-species interactions within SIHUMI-C, providing new insights into how broad-spectrum antimicrobials might fail to control targeted species in complex gut microbial communities. These findings highlight the need to mitigate off-target effects in complex gut microbiomes when developing bacteriocin-based therapies with potential clinical implications for infectious disease treatment.

Clinical Outcome Differences in Mucinous Versus Non-Mucinous Colonic Adenocarcinoma: A Comparative Study.

Background/Objectives: Colon cancer is one of the main causes of cancer-related mortality worldwide. Among its histopathological subtypes, mucinous adenocarcinoma (MAC) is characterized by a more aggressive behavior than non-mucinous adenocarcinoma (non-MAC). This study aimed to compare the clinical outcomes and postoperative recovery between MAC and non-MAC cases in order to better understand the treatment implications and optimize therapeutic strategies. Methods: A retrospective cohort study was conducted on patients diagnosed and treated at the Bihor County Emergency Hospital between January 2019 and December 2022. Data were collected from the medical records. Patients were divided into two groups, based on the histopathological results: mucinous adenocarcinoma and non-mucinous adenocarcinoma. Statistical analysis included descriptive statistics, t-tests, Chi-square tests, and ANOVA where appropriate. Results: A total of 191 patients were enrolled in this study, grouped in 36 cases of MAC and 155 cases of non-MAC. No significant statistical differences were found regarding hematological parameters. However, MAC was associated with higher rates of local invasion and a predominant right-sided colonic location, necessitating more frequent right colectomies. The overall mortality rate was significantly higher for MAC, indicating its aggressive nature. Conclusions: MAC presents higher local invasion rates and overall mortality. The aggressiveness of MAC underscores the need for tailored treatment approaches to optimize patient outcomes. Future large-scale studies are recommended to validate these findings and refine the therapeutic strategies.

Physician knowledge, use, and perceptions of genetic biomarker testing for the management of patients with newly diagnosed advanced ovarian cancer: an international physician survey.

To explore physician-reported knowledge, use, and perceptions of genetic testing for advanced ovarian cancer management. Gynecology/oncology specialists (n = 390) in the US, Europe, Canada, Japan, and Australia completed an online survey spanning March 2021 to April 2022. Physician-reported breast cancer gene mutation (BRCAm) testing rates increased over the 2 years before the survey; most patients underwent testing in the preceding 6 months. Homologous recombination deficiency (HRD) genomic instability testing rates and physicians' confidence interpreting results remained relatively low. Genetic testing was driven by the associated treatment implications of the findings. Poor performance status, inadequate tissue, and patients' willingness to undergo testing were reported barriers to testing. Findings indicate that there is a need to improve both access to and information about HRD testing.

Increased SOX10, p16, and Cyclin D1 Immunoreactivity Differentiates MAP Kinase-activated Low-grade Gliomas From Piloid Gliosis.

Low-grade gliomas and reactive piloid gliosis can present with overlapping features on conventional histology. Given the large implications for patient treatment, there is a need for effective methods to discriminate these morphologically similar but clinically distinct entities. Using routinely available stains, we hypothesize that a limited panel including SOX10, p16, and cyclin D1 may be useful in differentiating mitogen-activated protein (MAP) kinase-activated low-grade gliomas from piloid gliosis. Reviewers blinded to clinical and pathologic data reviewed and quantified immunohistochemical expression patterns across 20 cases of piloid gliosis and 37 cases of MAP kinase-activated low-grade gliomas, including pilocytic astrocytoma and ganglioglioma. The majority of MAP kinase-activated low-grade glioma cases demonstrated extensive immunoreactivity for at least 2 of the 3 immunohistochemical markers, whereas none of the gliosis cases demonstrated significant immunoreactivity for more than one individual immunohistochemical marker. SOX10 and p16 demonstrated the highest individual sensitivity whereas cyclin D1 demonstrated the highest individual specificity to discriminate neoplastic from nonneoplastic cases in this cohort. A composite panel score based on significant immunoreactivity of at least 2 of the 3 markers provided specificity and a positive predictive value of 100% in differentiating MAP kinase-activated low-grade glioma from gliosis, as 0/20 (0%) of gliosis cases were scored positive compared with 24/37 (65%) of MAP kinase-activated low-grade glioma cases. We conclude that while the immunoreactivity of these markers may be suggestive of a low-grade glioma diagnosis, SOX10, p16, and cyclin D1 should be applied in combination to maximize diagnostic value.

Subchondral insufficiency fracture of the knee.

Subchondral insufficiency fractures of the knee (SIFK) are arelatively common cause of knee pain, particularly in middle-aged and older adults. The SIFK is atype of stress fracture that occurs when excessive and repetitive or supraphysiologic loads are applied to subchondral bone [1]. Historically, this type of fracture was termed spontaneous osteonecrosis of the knee (SONK) until advances in MRI identified underlying fractures as well as meniscal deficiency as likely attributable etiologies. Consequently, SIFK has replaced SONK as the more appropriate term to refer to this category of conditions, with SONK now viewed as an advanced SIFK lesion. With greater availability of MRI, SIFK has been more frequently recognized and not as commonly mistaken for knee osteoarthritis as it had been in the past, with important implications for treatment and management of this condition.

Unraveling the Epigenetic Landscape of Neurosyphilis: Implications for Diagnosis, Treatment, and Long-term Management.

Unraveling the Epigenetic Landscape of Neurosyphilis: Implications for Diagnosis, Treatment, and Long-term Management.

Possible linking and treatment between Parkinson’s disease and inflammatory bowel disease: a study of Mendelian randomization based on gut–brain axis

BackgroundMounting evidence suggests that Parkinson’s disease (PD) and inflammatory bowel disease (IBD) are closely associated and becoming global health burdens. However, the causal relationships and common pathogeneses between them are uncertain. Furthermore, they are uncurable. Thus, we aimed to identify the causal relationships and novel therapeutic targets shared between them based on their common pathophysiological mechanisms in gut–brain-axis (GBA).MethodsA meta-analysis on bidirectional Mendelian randomization (MR) utilizing various datasets was performed to estimate their causal relationship. Then, pleiotropic analysis under the composite null hypothesis (PLACO) with functional mapping combined with annotation of genetic associations (FUMA) analysis were conducted to identify pleiotropic genes. Next, blood, brain and intestine expression quantitative trait locus (eQTL) were taken to perform drug-target MR finding common causal genes in two diseases. Colocalization analysis ensured the eQTLs of corresponding gene colocalized with disease. Enrichment analysis and protein‒protein interaction (PPI) network were done to explore common pathogenesis pathways. Genes passed all analysis were regarded as drug targets.ResultsOur MR meta-analysis revealed the bidirectional causal relationship between diseases, with combined ORs for PD on IBD, CD, UC (1.050 [95% CI 1.014–1.086], 1.044 [95% CI 0.995–1.095], 1.063 [95% CI 1.016–1.120]); for IBD, CD, UC on PD (1.003 [95% CI 0.973–1.034], 1.035 [95% CI 1.004–1.067], 1.008 [95% CI 0.977–1.040]). Overall, 277, 216 and 201 genes were identified as pleiotropic genes between PD and IBD, CD, UC. Total of 733 genes were classified as tier 3 (found in only one tissue) druggable targets, 57 as tier 2 (found in two tissues, 51 protein-coding genes) and 9 as tier 3 (found in three tissues). Among 60 protein-coding druggable targets over tier 2, 18 overlapped with pleiotropic genes and enriched in mitochondria, antigen presentation, processing and immune cell regulation pathways. Three druggable genes (LRRK2, RAB29 and HLA-DQA2) passed colocalization analysis. LRRK2 and RAB29 were reported to be pleiotropic genes, and RAB29 and HLA-DQA2 were reported for the first time as potential drug targets.ConclusionsThis study established a reliable causal relationship, possible shared drug targets and common pathogenesis pathways of two diseases, which had important implications for intervention and treatment of two diseases simultaneously.

Identification of clinicopathological-specific driver gene and genetic subtyping of colorectal cancer.

This study analyzed targeted sequencing data from 6530 tissue samples from patients with metastatic Chinese colorectal cancer (CRC) to identify low mutation frequency and subgroup-specific driver genes, using three algorithms for overall CRC as well as across different clinicopathological subgroups. We analyzed 425 cancer-related genes, identifying 101 potential driver genes, including 36 novel to CRC. Notably, some genes demonstrated subgroup specificity; for instance, ERBB4 was found as a male-specific driver gene and mutations of ERBB4 only influenced the prognosis of male patients with CRC. This sex disparity of ERBB4 was validated in an independent large-scale Memorial Sloan Kettering Cancer Center CRC cohort with 2444 samples. Furthermore, using network-based stratification based on protein-protein interaction, we classified the microsatellite stable (MSS) and unstable (MSI) CRCs into six and three major subtypes, respectively, each showing unique phenotypes and prognoses. In MSS CRC, cluster 5 (APCAMER1-KRAS) and cluster 2 (RNF43-BRAF-PIK3CA) were predominant, and cluster 5 showed a superior overall survival compared with cluster 2. This extensive heterogeneity in driver gene mutations underscores the complexity of CRC and suggests significant implications for treatment and prognostic assessments.

Germline and Somatic Genomic Testing for Metastatic Prostate Cancer: ASCO Guideline.

To evaluate evidence on germline and somatic genomic testing for patients with metastatic prostate cancer and provide recommendations. A systematic review by a multidisciplinary panel with patient representation was conducted. The PubMed database was searched from January 2018 to May 2024. Articles were selected for inclusion if they reported on patients with metastatic prostate cancer who received a germline or somatic genomic test and/or made comparisons between those tests, reported detection rates, prognostic information, or treatment implications. A total of 1,713 papers were identified in the literature search. After applying the eligibility criteria, 14 remained: eight systematic reviews and six clinical trials. Patients with metastatic prostate cancer should undergo both germline and somatic DNA sequencing using panel-based assays. These tests can guide the use of poly(ADP-ribose) polymerase inhibitors, which have a survival benefit in metastatic castration-resistant prostate cancer. In addition, germline testing may have screening implications for additional cancers for patients and cascade testing implications for family members. The data supporting when to perform repeat testing and optimal tissue type to use (eg, primary tumor v metastatic biopsy versus circulating tumor DNA [ctDNA] testing) are more limited, but this panel recommends considering retesting in patients whose results were previously negative or uninformative, and to consider either a metastatic biopsy or ctDNA when a significant change in clinical status occurs. Next-generation genomic sequencing findings that are associated with prognostic only (and not predictive) value should not be used to guide treatment outside of a clinical trial.Additional information is available at www.asco.org/genitourinary-cancer-guidelines.

Resolving heterogeneity of early-onset major depressive disorder through individual differential structural covariance network analysis.

Early-onset major depressive disorder (EO-MDD) is characterized by its significant heterogeneity, hindering progress in research. Traditional case-control studies, like group-level structural covariance network, struggle to capture individual heterogeneity among EO-MDD patients. In this study, T1-weighted structural magnetic resonance imaging was obtained from 185 participants, including 103 EO-MDD patients and 82 healthy controls. A subject-level individual differential structural covariance network (IDSCN) was constructed for each patient based on the concept of normative model. Semi-supervised clustering algorithms were then employed to classify EO-MDD subtypes, followed by validation analyses to assess clustering stability. Our study identified two neuroanatomical subtypes. The low-covariance subtype is characterized by significant neural maturation gaps across the whole brain and more pronounced anxiety somatization symptoms. Conversely, the high-covariance subtype demonstrates simultaneous mature of brain structures. Our findings provide valuable insights into the neuroanatomical heterogeneity of EO-MDD patients, highlighting the importance of considering individual symptom profiles in subtype classification. These findings have substantial clinical implications for personalized treatment and precision medicine, offering more effective treatment choices and accurate diagnoses.

A Sequencing Overview of Malignant Peripheral Nerve Sheath Tumors: Findings and Implications for Treatment.

Malignant peripheral nerve sheath tumors (MPNSTs) are rare but aggressive malignancies with a low 5-year survival rate despite current treatments. MPNSTs frequently harbor mutations in key genes such as NF1, CDKN2A, TP53, and PRC2 components (EED or SUZ12) across different disease stages. With the rapid advancement of high-throughput sequencing technologies, the molecular characteristics driving MPNST development are becoming clearer. This review summarizes recent sequencing studies on peripheral nerve sheath tumors, including plexiform neurofibromas (PNs), atypical neurofibromatous neoplasm with uncertain biologic potential (ANNUBP), and MPNSTs, highlighting key mutation events in tumor progression from the perspectives of epigenetics, transcriptomics, genomics, proteomics, and metabolomics. We also discuss the therapeutic implications of these genomic findings, focusing on preclinical and clinical trials targeting these alterations. Finally, we conclude that overcoming tumor resistance through combined targeted therapies and personalized treatments based on the molecular characteristics of MPNSTs will be a key direction for future treatment strategies.

An Electroglottographic and Acoustic Study on Mandarin Speech in Male Heroin Users.

Drug abuse can cause severe damage to the human speech organs. The vocal folds are one of the important speech organs that produce voice through vibration when airflow passes through. Previous studies have reported the negative effects of drugs on speech organs, including the vocal folds, but there is still limited research on relevant field. Therefore, the current study recruited 25 heroin users and 30 healthy controls with no history of drug use. Electroglottography and speech signals of 26 target sentences were collected from all participants. The results of the current study showed that the heroin group exhibited higher DFx1 and H1-A3, and lower DAx1 and jitter, and lower F1 frequency for /a/ and F2 frequency for /i/, but higher F2 frequency for /u/ compared to the no drug group. These findings suggested the presence of vocal hoarseness, frequency and amplitude distributions that differed from the norm, and a limited range of tongue movement in the heroin group. This study not only enhances the understanding of the effects of heroin on speech production but also has implications for detoxification treatment and speech rehabilitation for drug users.

The Association Between Peritraumatic Dissociation and Race-Based Trauma Symptoms: The Role of Negative Cognitions

ABSTRACT Peritraumatic dissociation is a risk factor for the development of Post-Traumatic Stress Disorder (PTSD). Per the cognitive model of PTSD and empirical research, cognitive appraisals mediate the relationship between peritraumatic dissociation and PTSD. Racial trauma has recently been conceptualized as a psychological sequelae to racism and discrimination that involves a posttraumatic stress reaction to experiences of racism and discrimination. Given the theoretical parallels between PTSD and racial trauma, we hypothesized that negative cognitions would intervene in the relationship between peritraumatic dissociation and racial trauma. To test this hypothesis, we examined whether negative cognitions about the self and the world and self-blame intervened in the relationship between peritraumatic dissociation and racial trauma among 220 minoritized participants. The results indicated that negative views about the self (b = .24) and the world (b = .18), but not self-blame intervened in the relationship between peritraumatic dissociations and racial trauma. These findings provide some insight regarding how negative cognitions relate to peritraumatic dissociations and racial trauma, allowing for a discussion of potential treatment implications.

Alcohol Use Disorder and the Gut-Brain Axis: A Narrative Review of the Role of Gut Microbiota and Implications for Treatment.

Alcohol use disorder (AUD) affects millions of people worldwide and can lead to deleterious physical and social consequences. Recent research has highlighted not only the effect of alcohol on the gut microbiome, but also the role of the gut microbiome and the gut-brain axis in the development and maintenance of alcohol use disorder. This review provides an overview of the reciprocal relationship between alcohol consumption and the gut microbiome, including the effects of alcohol on gut microbial composition, changes in gut microbial metabolites in response to alcohol consumption, and how gut microbial metabolites may modulate alcohol use behavior. We also discuss the gut-mediated mechanisms of neuroinflammation that contribute to and result from AUD, including disruption of the intestinal barrier, toll-like receptor signaling, and the activation of glial cells and immune cells. Finally, we review the current evidence on gut microbial-directed therapies for AUD and discuss the implications of this research for our understanding of the pathophysiology of AUD and future research directions.

Changes in Subjective Cognitive and Social Functioning in Parkinson's Disease from Before to During the COVID-19 Pandemic.

Background/Objectives: Social isolation and health-related consequences of the COVID-19 pandemic may have significantly impacted quality of life in people with Parkinson's disease (PwPD). The effect of the COVID-19 pandemic specifically on subjective cognition and social functioning in PwPD is poorly understood. We conducted a longitudinal analysis of changes in subjective cognitive and social functioning in PwPD before (T1, 2017-2019) and during (T2, 2021) the COVID-19 pandemic. Methods: At T1, 347 PwPD completed online surveys. At T2, 123 of them (54 males, 69 females) responded to follow-up questionnaires including Quality of Life in Neurological Disorders (Neuro-QoL) subscales, Beck Depression Inventory-II, Parkinson's Anxiety Scale, motor and non-motor experiences of daily living from the MDS-Unified Parkinson's Disease Rating Scale, and the Coronavirus Impact Scale. Results: T1-T2 declines in subjective cognition and social functioning both were correlated with more anxiety, fatigue, and motor symptoms. Additionally, declines in subjective cognition correlated with depression, and with decline in social functioning. Women reported greater COVID-19 impact than men, unrelated to cognition and social functioning; in men, personal experience with COVID-19 was associated with decline in subjective cognition. Conclusions: Our finding that subjective cognition and social functioning are associated with different motor and non-motor symptoms of PD suggests that the impacts of PD on subjective cognition and social functioning are complex, which has important implications for treatment.

Mechanisms Underlying Iron Deficiency-Induced Cardiac Disorders: Implications for Treatment.

Two billion people worldwide suffer from anemia, which can lead to the onset of cardiac disorders; nevertheless, the precise mechanisms remain unclear. There are at least three distinct mechanisms by which iron deficiency (ID) contributes to the development of cardiac disorders. First, ID increases concentrations of intact fibroblast growth factor-23 (iFGF-23), which promotes left ventricular hypertrophy. Additionally, individuals with ID typically have low circulating levels of vitamin D and an increased body burden of cadmium (Cd). Both factors-high Cd levels and a lack of vitamin D-elevate the risk of various cardiac disorders. Cd is transported in the body via transferrin and as non-transferrin-bound cadmium (NTBCd), with around 50% carried by transferrin. Transferrin-bound Cd is internalized into cells through the transferrin receptor 1 (TfR1), whereas NTBCd uptake occurs via receptors involved in iron transport, such as divalent metal transporter 1 (DMT1), ZIP8, and ZIP14. These receptors, expressed in tissues like the myocardium, contribute to Cd accumulation in the heart. In cases of coronary artery disease, regions of the heart affected by hypoxia, due to reduced blood flow, overexpress TfR1, DMT1, ZIP8, and ZIP14. This increases the uptake of Cd into cardiomyocytes. Cd, once inside the cells, damages mitochondria through oxidative stress, lipid peroxidation, and DNA alterations, leading to cell death. Once destroyed, cardiomyocytes release intracellular potassium which can potentially cause fatal arrhythmia. Cardiac iron bioaccumulation is primarily influenced by two factors: blood iron concentrations and the density of TfR1. Numerous studies have explored the potential benefits of iron supplementation, with varying results. We hypothesize that the extent of beneficial effects from iron supplementation may depend on the presence of specific comorbidities, such as chronic kidney disease or hyperaldosteronism. This hypothesis is based on the observation that certain hormones, including aldosterone and noradrenaline, downregulate the expression of TfR1. Therefore, we propose that co-treatment with iron and aldosterone antagonists could enhance cardiac iron uptake and improve the overall effectiveness of the therapy. Additionally, vitamin D supplementation prior to the onset of disease and chelation therapy after diagnosis could provide some benefits.

Transcription factor specificity protein (SP) family in renal physiology and diseases.

Dysregulated specificity proteins (SPs), members of the C2H2 zinc-finger family, are crucial transcription factors (TFs) with implications for renal physiology and diseases. This comprehensive review focuses on the role of SP family members, particularly SP1 and SP3, in renal physiology and pathology. A detailed analysis of their expression and cellular localization in the healthy human kidney is presented, highlighting their involvement in fatty acid metabolism, electrolyte regulation, and the synthesis of important molecules. The review also delves into the diverse roles of SPs in various renal diseases, including renal ischemia/reperfusion injury, diabetic nephropathy, renal interstitial fibrosis, and lupus nephritis, elucidating their molecular mechanisms and potential as therapeutic targets. The review further discusses pharmacological modulation of SPs and its implications for treatment. Our findings provide a comprehensive understanding of SPs in renal health and disease, offering new avenues for targeted therapeutic interventions and precision medicine in nephrology.