Screening inflammatory protein biomarkers on premature infants with necrotizing enterocolitis.

OBJECTIVE: This study aimed to explore potential inflammatory biomarkers for early prediction of necrotizing enterocolitis (NEC) in premature infants. METHODS: Plasma samples were collected from premature infants with NEC (n = 30), sepsis (n = 29), and controls without infection (n = 29). The 92 inflammatory-related proteins were assessed via high-throughput OLINK proteomics platform. RESULTS: There were 11 inflammatory proteins that significate differences (p < 0.05) among NEC, sepsis and control preterm infants, which include IL-8, TRAIL, IL-24, MMP-10, CCL20, CXCL1, OPG, TSLP, MCP-4, TNFSF14 and LIF. A combination of these 11 proteins could serve as differential diagnosis between NEC and control infants (AUC = 0.972), or between NEC and sepsis infants (AUC = 0.881). Furthermore, the combination of IL-8, OPG, MCP-4, IL-24, LIF and CCL20 could distinguish Stage II and III of NEC (AUC = 0.977). Further analysis showed the combination of IL-8, IL-24 and CCL20 have the best prediction value for NEC and control (AUC = 0.947), NEC and sepsis (AUC = 0.838) and different severity of NEC (AUC = 0.842). CONCLUSION: Inflammatory proteins were different expressed in premature infants with NEC compared with controls or sepsis. Combining these proteins provide a higher diagnostic potential for preterm NEC infants.

Hematoma cavity separation and neomembrane thickness are potential triggers of recurrence of chronic subdural hematoma.

BACKGROUND: Chronic subdural hematoma (CSDH) is the anomalous and encapsulated accumulation of fluid of complex origin consisting of old blood, mostly or totally liquified and cerebrospinal fluid (CSF) in the subdural space usually after a head injury in the elderly. Almost all the research on surgical techniques and endoscopic assisted evacuation of CSDH focused on the just the evacuation and not abnormal anatomical structures that causes recurrences. OBJECTIVES: We investigated abnormal anatomical structures that triggers recurrence of CSDH during craniotomy as well as burr-hole craniostomy with endoscopic assistance. MATERIALS AND METHODS: We retrospectively analyzed all patients with CSDH who underwent craniostomy and burr-hole craniotomy with endoscopic assisted evacuation of hematoma between April 2017 and November 2020 at our institution. Clinical data obtained was categorized into patient-related, radiology as well as surgery and endoscopic evaluations. RESULTS: A total of 143 patients (109 men and 34 women) aged 43-94 years (mean age, 68.35 years) with CSDH were included in this study. We observed a recurrence rate of 4.9% (7/143). Recurrences occurred between 2 and 6 months after the operation in patients with recurrences. Our data revealed that, age, hypertension, history of injury, diabetes, antiplatelet or anticoagulant use were not associated with hematoma recurrence. Nevertheless, all the patients with recurrence of hematoma were males. Interestingly, our univariate and multivariate analyses found neomembrane thickness and hematoma cavity separation as independent risk factors (OR,45.822; 95% CI,2.666-787.711; p = 0.008) for the recurrence of CSDH (p < 0.05). Also, we observed thickened membranes connecting/separating the dura and the thickened arachnoid/pia matters in all the 7 patients with hematoma recurrence. CONCLUSIONS: The treatment of patients with CSDH ought to include the identification and resection of abnormal thickened membranes connecting/separating the dura and the thickened arachnoid/pia matters to avoid recurrence. Comparatively, endoscopy showed hematoma cavity separation or neomembrane thickness just as seen during craniotomy.

Exploring the Pivotal Immunomodulatory and Anti-Inflammatory Potentials of Glycyrrhizic and Glycyrrhetinic Acids.

Licorice extract is a Chinese herbal medication most often used as a demulcent or elixir. The extract usually consists of many components but the key ingredients are glycyrrhizic (GL) and glycyrrhetinic acid (GA). GL and GA function as potent antioxidants, anti-inflammatory, antiviral, antitumor agents, and immuneregulators. GL and GA have potent activities against hepatitis A, B, and C viruses, human immunodeficiency virus type 1, vesicular stomatitis virus, herpes simplex virus, influenza A, severe acute respiratory syndrome-related coronavirus, respiratory syncytial virus, vaccinia virus, and arboviruses. Also, GA was observed to be of therapeutic valve in human enterovirus 71, which was recognized as the utmost regular virus responsible for hand, foot, and mouth disease. The anti-inflammatory mechanism of GL and GA is realized via cytokines like interferon-γ, tumor necrotizing factor-α, interleukin- (IL-) 1ß, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, and IL-17. They also modulate anti-inflammatory mechanisms like intercellular cell adhesion molecule 1 and P-selectin, enzymes like inducible nitric oxide synthase (iNOS), and transcription factors such as nuclear factor-kappa B, signal transducer and activator of transcription- (STAT-) 3, and STAT-6. Furthermore, DCs treated with GL were capable of influencing T-cell differentiation toward Th1 subset. Moreover, GA is capable of blocking prostaglandin-E2 synthesis via blockade of cyclooxygenase- (COX-) 2 resulting in concurrent augmentation nitric oxide production through the enhancement of iNOS2 mRNA secretion in Leishmania-infected macrophages. GA is capable of inhibiting toll-like receptors as well as high-mobility group box 1.

Retraction Note to: Bio­HMGB1 from breast cancer contributes to M­MDSC differentiation from bone marrow progenitor cells and facilitates conversion of monocytes into MDSC­like cells.

The Editor-in-Chief has retracted this article.

Tumor-associated hemorrhage in patients with vestibular schwannoma.

OBJECT: Intratumoral hemorrhage (ITH) associated with vestibular schwannomas (VS) is very rare. We retrospectively analyzed VS patients presenting with ITH in our department to further gain a better understanding of this uncommon clinical presentation. METHODS: We treated seven patients who had VS presenting with ITH between January 2012 and June 2017. All the patients had preoperative computed tomography (CT), computed tomography angiography (CTA), and magnetic resonance imaging(MRI) done which aided in the radiological diagnosis as well as postoperative MRI to confirm the resection extent of the VS. Continuous electrophysiological monitoring of cranial nerves was carried out during surgery. RESULTS: Of the seven patients, three were male and four were female. Their ages ranged from 42 to 71 years (average age, 57.4 years). Two patients reported a history of hypertension. Sudden onset or rapid worsening of clinical symptoms occurred in five patients at time of hemorrhage. The mean diameter of the lesions was 4.1 cm (range, 3.0-5.0 cm). No patient had a pretreatment of stereotactic radiosurgery. Gross total resection was achieved in four cases and subtotal resection in three cases. There were no surgery-related neurological deficits but one patient died 18 days after surgery. Follow-up visits were scheduled at 6 months postoperatively and two patients had tumor recurrence and received stereotactic radiosurgery again. CONCLUSIONS: The incidence of ITH in VS is relatively rare and hypertension may highly correlate with ITH in VS. In comparison with peritumoral adhesion caused by chronic inflammation in multicystic VS with microhemorrhage,ITH caused by acute massive hemorrhage will not increase the extent of peritumoral adhesion immediately. The prognosis of surgery for patients with acute hemorrhagic VS may be better than that for microhemorrhage in multicystic VS. Besides, timely microsurgical treatment is also important to relieve symptoms.

Giant intradural cervical spine arteriovenous malformations - A case and review of literature.

INTRODUCTION: Spinal arteriovenous malformations (SAVMs) are very rare and can be very challenging to treat since none of the therapeutic options does provide a definitive cure to these lesions. We believe that incorporation of intraoperative angiography during surgery in a hybrid theatre can help achieve a better cure. CASE PRESENTATION: We present a 45 years old woman with three (3) years history of weakness and ten (10) days' history of acute pain in right upper extremity. Magnetic resonance angiography (MRA) of the cervical segment of spinal cord revealed tortuous vascular masses from foramen magnum to the inferior margin of fourth cervical (C4) vertebral. Spinal digital subtracting angiography (DSA) confirmed vascular malformation at the cervical segment of the spinal cord with their origin from bilateral posterior spinal arteries. She was successfully operated on with the aid of intraoperative angiography without any neurological deficient. CONCLUSION: Spinal angiography is the gold standard for all-inclusive assessment of SAVMs. Surgery and endovascular techniques equally have key therapeutic valves in treatment of SAVMs but a combination of the two gives a more accurate and reliable cure to this disorder.

Bio-HMGB1 from breast cancer contributes to M-MDSC differentiation from bone marrow progenitor cells and facilitates conversion of monocytes into MDSC-like cells.

Myeloid-derived suppressor cells (MDSC) constitute the major cell population that regulates immune responses. They are known to accumulate in tumors, chronic inflammatory and autoimmune diseases. Previous data indicate that high mobility group box 1(HMGB1) facilitates MDSC differentiation from bone marrow, suppresses NK cells, CD4+ and CD8+ T cells and is involved in cancer development. However, it remains unclear what potential mechanisms of HMGB1 facilitate MDSC differentiation. In the present work, we clearly demonstrate that HMGB1 secreted by cancer cells is N-glycosylated at Asn37, which facilitates monocytic (M)-MDSC differentiation from bone marrow via the p38/NFκB/Erk1/2 pathway and also contributes to conversion of monocytes into MDSC-like cells; HMGB1 blockade by a monoclonal antibody against the HMGB1 B box obviously reduced the accumulation of M-MDSC in tumor-bearing mice, delaying tumor growth and development; additionally, MDSC expansion and HMGB1 up-regulation were also found in breast cancer patients. All these data indicate that HMGB1 might be a potential tumor immunotherapy target.

The pivotal role of irradiation-induced apoptosis in the pathogenesis and therapy of medulloblastoma.

BACKGROUND: Medulloblastoma (MB) is a rare primitive neuroectodermal tumors originating from the cerebellum. MB is the most common malignant primary brain tumor of childhood. MB originates from neural precursor cells in distinctive regions of the rhombic lip, and their maturation occurs in the cerebellum or the brain stem during embryonal development. Also, apoptosis is a programmed cell death associated with numerous physiological as well as pathological regulations. RECENT FINDINGS: Irradiation (IR)-induce apoptosis triggers cell death, with or without intervening mitosis within a few hours of IR and these share different morphologic alteration such as, loss of normal nuclear structure as well as degradation of DNA. Moreover, MB is strikingly sensitive to DNA-damaging therapies and the role of apoptosis a key treatment modality. Furthermore, in MB, the apoptotic pathways are made up of several triggers, modulators, as well as effectors. Notably, IR-induced apoptotic mechanisms in MB therapy are very complex and they either induce radiosensitivity or inhibit radioresistance leading to potential effective treatment strategies for MB. CONCLUSION: This review explicitly explores the pivotal roles of IR-induced apoptosis in the pathogenesis and therapy of MB.

Elucidating the pivotal molecular mechanisms, therapeutic and neuroprotective effects of lithium in traumatic brain injury.

INTRODUCTION: Traumatic brain injury (TBI) refers to damage to brain tissue by mechanical or blunt force via trauma. TBI is often associated with impaired cognitive abilities, like difficulties in memory, learning, attention, and other higher brain functions, that typically remain for years after the injury. Lithium is an elementary light metal that is only utilized in salt form due to its high intrinsic reactivity. This current review discusses the molecular mechanisms and therapeutic and neuroprotective effects of lithium in TBI. METHOD: The "Boolean logic" was used to search for articles on the subject matter in PubMed and PubMed Central, as well as Google Scholar. RESULTS: Lithium's therapeutic action is extremely complex, involving multiple effects on gene secretion, neurotransmitter or receptor-mediated signaling, signal transduction processes, circadian modulation, as well as ion transport. Lithium is able to normalize multiple short- as well as long-term modifications in neuronal circuits that ultimately result in disparity in cortical excitation and inhibition activated by TBI. Also, lithium levels are more distinct in the hippocampus, thalamus, neo-cortex, olfactory bulb, amygdala as well as the gray matter of the cerebellum following treatment of TBI. CONCLUSION: Lithium attenuates neuroinflammation and neuronal toxicity as well as protects the brain from edema, hippocampal neurodegeneration, loss of hemispheric tissues, and enhanced memory as well as spatial learning after TBI.

Advances in synthetic lethality modalities for glioblastoma multiforme.

Glioblastoma multiforme (GBM) is characterized by a high mortality rate, high resistance to cytotoxic chemotherapy, and radiotherapy due to its highly aggressive nature. The pathophysiology of GBM is characterized by multifarious genetic abrasions that deactivate tumor suppressor genes, induce transforming genes, and over-secretion of pro-survival genes, resulting in oncogene sustainability. Synthetic lethality is a destructive process in which the episode of a single genetic consequence is tolerable for cell survival, while co-episodes of multiple genetic consequences lead to cell death. This targeted drug approach, centered on the genetic concept of synthetic lethality, is often selective for DNA repair-deficient GBM cells with restricted toxicity to normal tissues. DNA repair pathways are key modalities in the generation, treatment, and drug resistance of cancers, as DNA damage plays a dual role as a creator of oncogenic mutations and a facilitator of cytotoxic genomic instability. Although several research advances have been made in synthetic lethality modalities for GBM therapy, no review article has summarized these therapeutic modalities. Thus, this review focuses on the innovative advances in synthetic lethality modalities for GBM therapy.

Giant Brain Arteriovenous Malformation Managed by Staged Embolizations and Surgical Resection with Satisfactory Outcome.

Spetzler-Martin grade V (>6 cm) arteriovenous malformations (AVMs) are traditionally considered inoperable. A 35-year-old man presented with repeated seizures for 7 years, and computed tomography arteriography and magnetic resonance imaging revealed left deep hemispheric AVM. A combination of embolization and surgical resection successfully achieved a cure of the patient. Well-equipped neurosurgery facilities can best manage selective Spetzler-Martin grade V AVMs with no neurologic deficits contrary to their traditionally inoperable concept. Successful surgery offers the patient a better quality of life.

Localized Congenital Cutis Verticis Gyrate with Skull Erosion.

Localized congenital cutis verticis gyrate (CVG) is rare and potentially risks skull involvement. A 23-year-old woman presented with a congenital scalp mass in the occipital region. Local thickening of her left occipital scalp with ridges and furrows was observed on examination. Head computed tomography scan showed a lytic area underneath the same area of the occipital calvarium. The mass was surgically removed due to the skull erosion and cosmetic reasons. Pathologic evaluation established CVG. Surgical excision is best for localized congenital CVG with skull erosion due to cosmetic reasons. Surgical excision was rewarding to the patient it allowed her to style her hair.

Hemifacial spasms triggered by compression of tortuous anterior inferior cerebellar artery loop on the facial nerve in the internal auditory canal: A case report.

RATIONALE: Hemifacial spasm (HFS) is triggered by neurovascular compression mostly at the root entry/exit zone of the facial nerve. HFS with the responsible blood vessel located in the internal auditory canal (IAC) is a very rare occurrence. In our case, the HFS was triggered by compression of the anterior inferior cerebellar artery (AICA) loop on the facial nerve in the IAC. PATIENT CONCERNS: A 27-year-old female presented with a 5-year history of right-sided facial twitching with no obvious course. The frequency and severity of the attacks increases when the patient was anxious or agitated which severely affected her quality of life. DIAGNOSIS: Preoperative 3D-TOF magnetic resonance imaging (MRI) evaluation of cranial nerves showed that the right AICA loop had a tortuous course within the IAC and compressed the facial nerve. INTERVENTION: Microvascular decompression (MVD) surgery was carried out to separate the tortuous AICA loop and facial nerve in the IAC using a Teflon pad. OUTCOMES: The abnormal muscle response disappeared intraoperatively and 2-years follow-up revealed no recurrence of her symptomatology. She is current well and go about her daily activities with no neurological deficits. LESSON: The attachment of the facial nerve to the tortuous AICA loop coupled with the pulsatile impulse of tortuous AICA loop may have resulted in the entrapment and compression of the CN VII in the IAC.

Lhermitte-Duclos disease with excessive calcification in a septuagenarian: A case report.

RATIONALE: Lhermitte-Duclos disease (LDD), or dysplastic cerebellar gangliocytoma (DCG), is a rare tumor originating from the cerebellar cortex. LDD is a benign neuroglial tumor with uncertain prognosis. Over 200 cases have been reported in the literature mostly in the form of case reports. Thus, we present a spectacular case of LDD with excessive calcification in a female septuagenarian. PATIENT CONCERNS: A 72-year-old female presented with progressive dizziness for 8 months and suffered a head and sacrococcygeal region injury 20 days prior to her admission in our neurosurgery department. DIAGNOSIS: Computed tomography scan showed a right nonspecific cerebellar mass with striated calcification. Magnetic resonance imaging revealed a right "tiger-striped" alteration of the cerebellar cortex. H&E staining revealed a low grade glial neural tumor which was consistent with the diagnosis of LDD or DCG. INTERVENTION: The lesion was total resected. OUTCOMES: The patient recovered well and the cerebellar dysfunctional symptoms subsided 3 months after the operation and 2 years follow-up revealed no recurrence of the lesion and no neurological deficits. LESION: We postulate that the calcification of LDD is age-related and the pathogenesis of disease often observed in young adulthood.

Posterior Inferior Cerebellar Artery Aneurysm Shaped Like a "Calabash Gourd" and Mimicking a Tumor.

Posterior inferior cerebellar artery aneurysms are likely to be fusiform, yet they hardly enlarge to mimic a tumor in the posterior fossa on radiology. They constitute about 3%-4% of all cerebral aneurysms. A 65-year-old woman presented with tremor in her right upper limb for 1 year and intermittent dizziness for 8 months. Interestingly, magnetic resonance imaging revealed 2 unanimously enhanced masses like mother and daughter located in the right cerebellum hemisphere. The lesion was resected via surgery, and histopathology established the diagnosis of an aneurysm. Her tremor and dizziness subsided 3 months after the surgery, and at her 2-year follow-up she was well with no further neurologic deficits.

Aflatoxin B1 induces infertility, fetal deformities, and potential therapies.

Aflatoxin B1 (AFB1) is a subsidiary poisonous metabolite, archetypally spawned by Aspergillus flavus and A. parasiticus, which are often isolated in warm or tropical countries across the world. AFB1 is capable of disrupting the functioning of several reproductive endocrine glands by interrupting the enzymes and their substrates that are liable for the synthesis of various hormones in both males and females. In men, AFB1 is capable of hindering testicular development, testicular degeneration, and reduces reproductive capabilities. In women, a direct antagonistic interaction of AFB1 with steroid hormone receptors influencing gonadal hormone production of estrogen and progesterone was responsible for AFB1-associated infertility. AFB1 is potentially teratogenic and is responsible for the development of malformation in humans and animals. Soft-tissue anomalies such as internal hydrocephalus, microphthalmia, cardiac defects, augmented liver lobes, reproductive changes, immune modifications, behavioral changes and predisposition of animals and humans to neoplasm development are AFB1-associated anomalies. Substances such as esculin, selenium, gynandra extract, vitamins C and E, oltipraz, and CDDO-Im are potential therapies for AFB1. Thus, this review elucidates the pivotal pathogenic roles of AFB1 in infertility, fetal deformities, and potential therapies because AFB1 toxicity is a key problem globally.

Genetic pathways in cerebral palsy: a review of the implications for precision diagnosis and understanding disease mechanisms.

ABSTRACT: Cerebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture. Patients with cerebral palsy are often only capable of limited activity, resulting from non-progressive disturbances in the fetal or neonatal brain. These disturbances severely impact the child's daily life and impose a substantial economic burden on the family. Although cerebral palsy encompasses various brain injuries leading to similar clinical outcomes, the understanding of its etiological pathways remains incomplete owing to its complexity and heterogeneity. This review aims to summarize the current knowledge on the genetic factors influencing cerebral palsy development. It is now widely acknowledged that genetic mutations and alterations play a pivotal role in cerebral palsy development, which can be further influenced by environmental factors. Despite continuous research endeavors, the underlying factors contributing to cerebral palsy remain are still elusive. However, significant progress has been made in genetic research that has markedly enhanced our comprehension of the genetic factors underlying cerebral palsy development. Moreover, these genetic factors have been categorized based on the identified gene mutations in patients through clinical genotyping, including thrombosis, angiogenesis, mitochondrial and oxidative phosphorylation function, neuronal migration, and cellular autophagy. Furthermore, exploring targeted genotypes holds potential for precision treatment. In conclusion, advancements in genetic research have substantially improved our understanding of the genetic causes underlying cerebral palsy. These breakthroughs have the potential to pave the way for new treatments and therapies, consequently shaping the future of cerebral palsy research and its clinical management. The investigation of cerebral palsy genetics holds the potential to significantly advance treatments and management strategies. By elucidating the underlying cellular mechanisms, we can develop targeted interventions to optimize outcomes. A continued collaboration between researchers and clinicians is imperative to comprehensively unravel the intricate genetic etiology of cerebral palsy.

Raney clip left behind the titanium mesh after cranial surgery: Case report.

RATIONALE: Raney clips are commonly used in neurosurgical procedures to hold the scalp in place and stop bleeding during surgery. The removal of Raney clips is often the last process during cranial surgery prior to the closure of skin incision. Thus, a Raney clip found underneath the titanium mesh resulting in fever is a very rare occurrence. PATIENT CONCERNS: An 18-year-old male patient underwent cranial surgery due to intracranial abscess in the frontal lobe and subsequently underwent frontal skull repair using titanium mesh during which a Raney clip was unintentional left underneath the titanium mesh resulting in fever. DIAGNOSIS: A thin-slice computed tomography (CT) scan was used to identify the Raney clip. INTERVENTION: A third surgery was performed to remove the Raney clip. OUTCOMES: The patient fever total resolved after the third surgery with no further neurological deficits and 2-years follow-up revealed the patient is well and go about his daily activities. LESSONS: It is crucial to ensure that all foreign objects are removed after the surgery by counting all instruments used at and after each step during the operation, including all Raney clips. This will help prevent complications and ensure the safety as well as the well-being of the patient.

The Pattern of Anemia in Pediatric Solid Tumors Prior to and after Chemotherapy- A Retrospective Cohort Study.

BACKGROUND: Solid pediatric tumors refer to cancers that affect children and adoles-cents, and they present unique challenges due to their distinct biological characteristics and their vulnerability to young patients. This study aims to shed light on addressing anemia and the causes of anemia in patients with solid pediatric tumors. MATERIALS AND METHODS: This retrospective cohort comprised 200 healthy children as controls and 235 patients with solid tumors. The study was conducted at first Affiliated Hospital of Zhengzhou University between January 2020 and June 2023. We evaluated different parameters of blood components in controls and patients with solid tumors such as medulloblastoma, neuroblastoma, rhabdomyosarcoma, germ cell tumors, hepatoblastoma and nephroblastoma before and patients with only these tumors 3 weeks after the first cycle of chemotherapy. Further, we evaluated the relationship between serum ferritin and the weight of patients and assessed the relationship be-tween anemia and metastasis to the bone marrow in patients with neuroblastoma and hepatoblas-toma. RESULTS: We observed various combinations of derangements in blood parameters such as hemo-globin, red blood cells, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscu-lar hemoglobin concentration, hematocrit, red cell distribution width, white blood cells, and plate-let in medulloblastoma, neuroblastoma, rhabdomyosarcoma, germ cell tumors, hepatoblastoma and nephroblastoma before and 3 weeks after first cycle of chemotherapy. We found a significant correlation between serum ferritin levels and weight in neuroblastoma patients who are ≤ 2 years (p = 0.022). Involvement of tumor cells in bone marrow correlates with decreased Hb levels in both neuroblastoma (CI = 93.21-106.68, p = 0.001) and hepatoblastoma (CI = 113.36-121.00, p = 0.001). CONCLUSION: Anemia may manifest as an early symptom in neuroblastoma, hepatoblastoma, and nephroblastoma. Also, anemia may be worse in patients with neuroblastoma and hepatoblastoma after chemotherapy and might warrant anemia therapy.

Elucidating the Focal Immunomodulatory Clues Influencing Mesenchymal Stem Cells in the Milieu of Intervertebral Disc Degeneration.

The intervertebral discs (IVDs) are a relatively mobile joint that interconnects vertebrae of the spine. Intervertebral disc degeneration (IVDD) is one of the leading causes of low back pain, which is most often related to patient morbidity as well as high medical costs. Patients with chronic IVDD often need surgery that may sometimes lead to biomechanical complications as well as augmented degeneration of the adjacent segments. Moreover, treatment modalities like rigid intervertebral fusion, dynamic instrumentation, as well as other surgical interventions are still controversial. Mesenchymal stem cells (MSCs) have exhibited to have immunomodulatory functions and the ability to differentiate into cartilage, making these cells possibly an epitome for IVD regeneration. Transplanted MSCs were able to repair IVDD back to the normal disc milieu via the activation of the generation of extracellular matrix (ECM) proteins such as aggrecan, proteoglycans and collagen types I and II. IVD milieu clues like, periostin, cluster of differentiation, tumor necrosis factor alpha, interleukins, chemokines, transforming growth factor beta, reactive oxygen species, toll-like receptors, tyrosine protein kinase receptor and disialoganglioside, exosomes are capable of influencing the MSCs during treatment of IVDD. ECM microenvironment clues above have potentials as biomarkers as well as accurate molecular targets for therapeutic intervention in IVDD.